ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.1111G>C (p.Glu371Gln)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000179.3(MSH6):c.1111G>C (p.Glu371Gln)
Variation ID: 1710950 Accession: VCV001710950.4
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p16.3 2: 47799094 (GRCh38) [ NCBI UCSC ] 2: 48026233 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Oct 22, 2022 May 1, 2024 Mar 15, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000179.3:c.1111G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Glu371Gln missense NM_001281492.2:c.721G>C NP_001268421.1:p.Glu241Gln missense NM_001281493.2:c.205G>C NP_001268422.1:p.Glu69Gln missense NM_001281494.2:c.205G>C NP_001268423.1:p.Glu69Gln missense NM_001406795.1:c.1207G>C NP_001393724.1:p.Glu403Gln missense NM_001406796.1:c.1111G>C NP_001393725.1:p.Glu371Gln missense NM_001406797.1:c.814G>C NP_001393726.1:p.Glu272Gln missense NM_001406798.1:c.1111G>C NP_001393727.1:p.Glu371Gln missense NM_001406799.1:c.586G>C NP_001393728.1:p.Glu196Gln missense NM_001406800.1:c.1111G>C NP_001393729.1:p.Glu371Gln missense NM_001406801.1:c.814G>C NP_001393730.1:p.Glu272Gln missense NM_001406802.1:c.1207G>C NP_001393731.1:p.Glu403Gln missense NM_001406803.1:c.1111G>C NP_001393732.1:p.Glu371Gln missense NM_001406804.1:c.1033G>C NP_001393733.1:p.Glu345Gln missense NM_001406805.1:c.814G>C NP_001393734.1:p.Glu272Gln missense NM_001406806.1:c.586G>C NP_001393735.1:p.Glu196Gln missense NM_001406807.1:c.586G>C NP_001393736.1:p.Glu196Gln missense NM_001406808.1:c.1111G>C NP_001393737.1:p.Glu371Gln missense NM_001406809.1:c.1111G>C NP_001393738.1:p.Glu371Gln missense NM_001406811.1:c.205G>C NP_001393740.1:p.Glu69Gln missense NM_001406812.1:c.205G>C NP_001393741.1:p.Glu69Gln missense NM_001406813.1:c.1117G>C NP_001393742.1:p.Glu373Gln missense NM_001406814.1:c.205G>C NP_001393743.1:p.Glu69Gln missense NM_001406815.1:c.205G>C NP_001393744.1:p.Glu69Gln missense NM_001406816.1:c.205G>C NP_001393745.1:p.Glu69Gln missense NM_001406817.1:c.1111G>C NP_001393746.1:p.Glu371Gln missense NM_001406818.1:c.814G>C NP_001393747.1:p.Glu272Gln missense NM_001406819.1:c.814G>C NP_001393748.1:p.Glu272Gln missense NM_001406820.1:c.814G>C NP_001393749.1:p.Glu272Gln missense NM_001406821.1:c.814G>C NP_001393750.1:p.Glu272Gln missense NM_001406822.1:c.814G>C NP_001393751.1:p.Glu272Gln missense NM_001406823.1:c.205G>C NP_001393752.1:p.Glu69Gln missense NM_001406824.1:c.814G>C NP_001393753.1:p.Glu272Gln missense NM_001406825.1:c.814G>C NP_001393754.1:p.Glu272Gln missense NM_001406826.1:c.943G>C NP_001393755.1:p.Glu315Gln missense NM_001406827.1:c.814G>C NP_001393756.1:p.Glu272Gln missense NM_001406828.1:c.814G>C NP_001393757.1:p.Glu272Gln missense NM_001406829.1:c.205G>C NP_001393758.1:p.Glu69Gln missense NM_001406830.1:c.814G>C NP_001393759.1:p.Glu272Gln missense NR_176257.1:n.1200G>C NR_176258.1:n.1200G>C NR_176259.1:n.1200G>C NR_176261.1:n.1200G>C NC_000002.12:g.47799094G>C NC_000002.11:g.48026233G>C NG_007111.1:g.20948G>C LRG_219:g.20948G>C LRG_219t1:c.1111G>C LRG_219p1:p.Glu371Gln - Protein change
- E196Q, E241Q, E272Q, E315Q, E345Q, E371Q, E373Q, E403Q, E69Q
- Other names
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- Canonical SPDI
- NC_000002.12:47799093:G:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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MSH6 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
9038 | 9344 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (1) |
criteria provided, single submitter
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Sep 27, 2022 | RCV002292237.1 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Mar 15, 2023 | RCV002434624.3 |
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
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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
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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
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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. |
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Uncertain significance
(Sep 27, 2022)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 5
Affected status: unknown
Allele origin:
germline
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St. Jude Molecular Pathology, St. Jude Children's Research Hospital
Accession: SCV002584670.1
First in ClinVar: Oct 22, 2022 Last updated: Oct 22, 2022 |
Comment:
The MSH6 c.1111G>C (p.Glu371Gln) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect … (more)
The MSH6 c.1111G>C (p.Glu371Gln) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with Lynch syndrome or constitutional mismatch repair deficiency. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. (less)
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Uncertain significance
(Mar 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV004357572.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces glutamic acid with glutamine at codon 371 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein … (more)
This missense variant replaces glutamic acid with glutamine at codon 371 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has not been identified 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)
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Uncertain significance
(Aug 18, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002748089.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.E371Q variant (also known as c.1111G>C), located in coding exon 4 of the MSH6 gene, results from a G to C substitution at nucleotide … (more)
The p.E371Q variant (also known as c.1111G>C), located in coding exon 4 of the MSH6 gene, results from a G to C substitution at nucleotide position 1111. The glutamic acid at codon 371 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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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. |
Citations for germline classification of this variant
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated May 01, 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.