Variant summary: MSH6 c.1729C>T (p.Arg577Cys) results in a non-conservative amino acid change located in the DNA mismatch repair protein MutS, connector domain (IPR007860) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 250210 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1729C>T has been reported in the literature in an individual affected with MSI stable colorectal cancer and in an individual with colorectal cancer who met at least one of the revised Bethesda guidelines, as well as in individuals affected with other cancers within the Lynch Syndrome tumor spectrum, without strong evidence for causality (e.g.Hampel_2008, Loizidou_2014, Paulo_2018, Barbosa_2020). In a large study evaluating breast cancer cases and controls in the Breast Cancer Association Consortium (BCAC), the variant was reported in 9/60466 cases, and in 4/53461 controls (Dorling_2021 through LOVD). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Nonpolyposis Colorectal Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32658311, 33008098, 18809606, 25133505, 29659569, 33471991). ClinVar contains an entry for this variant (Variation ID: 89218). Based on the evidence outlined above, the variant was classified as uncertain significance.
ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.1729C>T (p.Arg577Cys)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(14)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Conflicting classifications of pathogenicity
Uncertain significance(11); Benign(1); Likely benign(2)
Uncertain significance(11); Benign(1); Likely benign(2)
14
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000179.3(MSH6):c.1729C>T (p.Arg577Cys)
Variation ID: 89218 Accession: VCV000089218.36
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 2p16.3 2: 47799712 (GRCh38) [ NCBI UCSC ] 2: 48026851 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 24, 2015 Sep 16, 2024 Jul 31, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000179.3:c.1729C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Arg577Cys missense NM_001281492.2:c.1339C>T NP_001268421.1:p.Arg447Cys missense NM_001281493.2:c.823C>T NP_001268422.1:p.Arg275Cys missense NM_001281494.2:c.823C>T NP_001268423.1:p.Arg275Cys missense NC_000002.12:g.47799712C>T NC_000002.11:g.48026851C>T NG_007111.1:g.21566C>T LRG_219:g.21566C>T LRG_219t1:c.1729C>T LRG_219p1:p.Arg577Cys - Protein change
- R577C, R447C, R275C
- Other names
- p.R577C:CGC>TGC
- Canonical SPDI
- NC_000002.12:47799711:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00020 (G)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00005
The Genome Aggregation Database (gnomAD) 0.00010
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| MSH6 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
9153 | 9466 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
|
Jul 16, 2024 | RCV000115381.18 | |
| Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Mar 29, 2023 | RCV000409690.10 | |
| Benign (1) |
criteria provided, single submitter
|
Jan 24, 2024 | RCV000524118.17 | |
| Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Sep 1, 2023 | RCV000491847.23 | |
| Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Jul 31, 2024 | RCV003235029.10 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Mar 28, 2024 | RCV003466935.2 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jan 11, 2024 | RCV003997068.2 | |
| Likely benign (1) |
criteria provided, single submitter
|
Apr 9, 2024 | RCV003993789.1 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Feb 08, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003934342.2
First in ClinVar: Jun 24, 2023 Last updated: Apr 15, 2024 |
Comment:
Variant summary: MSH6 c.1729C>T (p.Arg577Cys) results in a non-conservative amino acid change located in the DNA mismatch repair protein MutS, connector domain (IPR007860) of the … (more)
Variant summary: MSH6 c.1729C>T (p.Arg577Cys) results in a non-conservative amino acid change located in the DNA mismatch repair protein MutS, connector domain (IPR007860) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 250210 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1729C>T has been reported in the literature in an individual affected with MSI stable colorectal cancer and in an individual with colorectal cancer who met at least one of the revised Bethesda guidelines, as well as in individuals affected with other cancers within the Lynch Syndrome tumor spectrum, without strong evidence for causality (e.g.Hampel_2008, Loizidou_2014, Paulo_2018, Barbosa_2020). In a large study evaluating breast cancer cases and controls in the Breast Cancer Association Consortium (BCAC), the variant was reported in 9/60466 cases, and in 4/53461 controls (Dorling_2021 through LOVD). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Nonpolyposis Colorectal Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32658311, 33008098, 18809606, 25133505, 29659569, 33471991). ClinVar contains an entry for this variant (Variation ID: 89218). Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
|
|
|
Likely benign
(Apr 09, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary nonpolyposis colon cancer
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV000837885.3
First in ClinVar: Oct 10, 2018 Last updated: Apr 15, 2024 |
|
|
|
Uncertain Significance
(Jan 11, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Lynch syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004837795.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
This missense variant replaces arginine with cysteine at codon 577 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces arginine with cysteine at codon 577 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with prostate (PMID: 29659569), ovarian (PMID: 33008098), breast (PMID: 33471991) and colorectal cancer (PMID: 18809606, 25133505). This variant has also been observed in healthy individuals in breast and pancreatic cancer case-control studies (PMID: 32980694, 33471991). This variant has been identified in 10/281608 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 8
|
|
|
Likely benign
(Sep 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000580218.7
First in ClinVar: Jun 25, 2017 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
|
Uncertain significance
(Mar 28, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Endometrial carcinoma
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004195557.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Uncertain significance
(Sep 25, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888249.2
First in ClinVar: Mar 13, 2019 Last updated: Jan 01, 2022 |
|
|
|
Uncertain significance
(Nov 01, 2021)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002535654.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The MSH6 c.1729C>T (p.R577C) has been reported in heterozygosity in at least two individuals with colorectal cancer (PMID: 25133505,18809606). It was also identified in at … (more)
The MSH6 c.1729C>T (p.R577C) has been reported in heterozygosity in at least two individuals with colorectal cancer (PMID: 25133505,18809606). It was also identified in at least one individual with prostate cancer (PMID: 29659569), and in at least one individual with ovarian cancer (PMID: 33008098). It has been reported in a large case-control study of breast cancer in 9/60466 cases and 4/53461 controls (PMID: 33471991). This variant was observed in 10/281608 chromosomes in the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). The variant has been reported in ClinVar (Variation ID: 89218). In silico tools suggest the impact of the variant on protein function is deleterious, though no microsatellite instability or MSH6 protein deficiency were seen in patients carrying this variant (PMID: 29659569, 33008098). The evidence is insufficient to meet ACMG/AMP criteria for classifying the variant as benign or pathogenic. Thus, the clinical significance of this variant is currently uncertain. (less)
|
|
|
|
Uncertain significance
(Dec 08, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Lynch syndrome 5
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000487932.2
First in ClinVar: Jan 06, 2017 Last updated: Dec 24, 2022 |
|
|
|
Uncertain significance
(Nov 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002010115.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
|
|
|
Uncertain significance
(Mar 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Lynch syndrome 5
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV004019030.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
|
|
|
Uncertain significance
(Mar 06, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000685222.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces arginine with cysteine at codon 577 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces arginine with cysteine at codon 577 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with prostate (PMID: 29659569), ovarian (PMID: 33008098), breast (PMID: 33471991) and colorectal cancer (PMID: 18809606, 25133505). This variant has also been observed in healthy individuals in breast and pancreatic cancer case-control studies (PMID: 32980694, 33471991). This variant has been identified in 10/281608 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
|
|
|
Benign
(Jan 24, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary nonpolyposis colorectal neoplasms
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000551178.10
First in ClinVar: Mar 24, 2015 Last updated: Feb 20, 2024 |
|
|
|
Uncertain significance
(Jul 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV005090481.1
First in ClinVar: Aug 04, 2024 Last updated: Aug 04, 2024 |
|
|
|
Uncertain significance
(Jul 16, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000149290.19
First in ClinVar: May 17, 2014 Last updated: Sep 16, 2024 |
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26333163, … (more)
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26333163, 18809606, 25133505, 26689913, 29659569, 33008098, 33471991, 21120944, 17531815, 36243179, 35449176, 33057194, 35980532, 35982159, 35534704) (less)
|
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Comment:
Comment:
This missense variant replaces arginine with cysteine at codon 577 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with prostate (PMID: 29659569), ovarian (PMID: 33008098), breast (PMID: 33471991) and colorectal cancer (PMID: 18809606, 25133505). This variant has also been observed in healthy individuals in breast and pancreatic cancer case-control studies (PMID: 32980694, 33471991). This variant has been identified in 10/281608 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Comment:
This missense variant replaces arginine with cysteine at codon 577 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with prostate (PMID: 29659569), ovarian (PMID: 33008098), breast (PMID: 33471991) and colorectal cancer (PMID: 18809606, 25133505). This variant has also been observed in healthy individuals in breast and pancreatic cancer case-control studies (PMID: 32980694, 33471991). This variant has been identified in 10/281608 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26333163, 18809606, 25133505, 26689913, 29659569, 33008098, 33471991, 21120944, 17531815, 36243179, 35449176, 33057194, 35980532, 35982159, 35534704)
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Variant summary: MSH6 c.1729C>T (p.Arg577Cys) results in a non-conservative amino acid change located in the DNA mismatch repair protein MutS, connector domain (IPR007860) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 250210 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1729C>T has been reported in the literature in an individual affected with MSI stable colorectal cancer and in an individual with colorectal cancer who met at least one of the revised Bethesda guidelines, as well as in individuals affected with other cancers within the Lynch Syndrome tumor spectrum, without strong evidence for causality (e.g.Hampel_2008, Loizidou_2014, Paulo_2018, Barbosa_2020). In a large study evaluating breast cancer cases and controls in the Breast Cancer Association Consortium (BCAC), the variant was reported in 9/60466 cases, and in 4/53461 controls (Dorling_2021 through LOVD). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Nonpolyposis Colorectal Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32658311, 33008098, 18809606, 25133505, 29659569, 33471991). ClinVar contains an entry for this variant (Variation ID: 89218). Based on the evidence outlined above, the variant was classified as uncertain significance.
Comment:
This missense variant replaces arginine with cysteine at codon 577 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with prostate (PMID: 29659569), ovarian (PMID: 33008098), breast (PMID: 33471991) and colorectal cancer (PMID: 18809606, 25133505). This variant has also been observed in healthy individuals in breast and pancreatic cancer case-control studies (PMID: 32980694, 33471991). This variant has been identified in 10/281608 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Comment:
This missense variant replaces arginine with cysteine at codon 577 of the MSH6 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with prostate (PMID: 29659569), ovarian (PMID: 33008098), breast (PMID: 33471991) and colorectal cancer (PMID: 18809606, 25133505). This variant has also been observed in healthy individuals in breast and pancreatic cancer case-control studies (PMID: 32980694, 33471991). This variant has been identified in 10/281608 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26333163, 18809606, 25133505, 26689913, 29659569, 33008098, 33471991, 21120944, 17531815, 36243179, 35449176, 33057194, 35980532, 35982159, 35534704)
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
| Germline pathogenic variant spectrum in 25 cancer susceptibility genes in Turkish breast and colorectal cancer patients and elderly controls. | Akcay IM | International journal of cancer | 2021 | PMID: 32658311 |
| Gene Panel Tumor Testing in Ovarian Cancer Patients Significantly Increases the Yield of Clinically Actionable Germline Variants beyond BRCA1/BRCA2. | Barbosa A | Cancers | 2020 | PMID: 33008098 |
| Genetic characterization of pancreatic cancer patients and prediction of carrier status of germline pathogenic variants in cancer-predisposing genes. | Mizukami K | EBioMedicine | 2020 | PMID: 32980694 |
| Targeted next generation sequencing identifies functionally deleterious germline mutations in novel genes in early-onset/familial prostate cancer. | Paulo P | PLoS genetics | 2018 | PMID: 29659569 |
| Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers. | Pritchard AL | PloS one | 2018 | PMID: 29641532 |
| Classification of Amino Acid Substitutions in Mismatch Repair Proteins Using PON-MMR2. | Niroula A | Human mutation | 2015 | PMID: 26333163 |
| The mutational spectrum of Lynch syndrome in cyprus. | Loizidou MA | PloS one | 2014 | PMID: 25133505 |
| Feasibility of screening for Lynch syndrome among patients with colorectal cancer. | Hampel H | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2008 | PMID: 18809606 |
Text-mined citations for rs542838372 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.