Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000179.3(MSH6):c.1144C>T (p.His382Tyr)

Help
Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(5)

Review status:
criteria provided, conflicting interpretations
Submissions:
6 (Most recent: Jun 17, 2021)
Last evaluated:
May 19, 2021
Accession:
VCV000089176.12
Variation ID:
89176
Description:
single nucleotide variant
Help

NM_000179.3(MSH6):c.1144C>T (p.His382Tyr)

Allele ID
94650
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2p16.3
Genomic location
2: 47799127 (GRCh38) GRCh38 UCSC
2: 48026266 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000002.12:g.47799127C>T
NG_007111.1:g.20981C>T
NM_000179.3:c.1144C>T MANE Select NP_000170.1:p.His382Tyr missense
... more HGVS
Protein change
H382Y, H80Y, H252Y
Other names
-
Canonical SPDI
NC_000002.12:47799126:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD) 0.00004
The Genome Aggregation Database (gnomAD) 0.00010
Links
ClinGen: CA008133
dbSNP: rs587779207
VarSome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter May 29, 2018 RCV000213163.3
Uncertain significance 1 criteria provided, single submitter Aug 29, 2016 RCV000411429.1
Uncertain significance 1 criteria provided, single submitter Oct 21, 2020 RCV000627690.5
Uncertain significance 1 criteria provided, single submitter May 19, 2021 RCV001255541.2
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Oct 6, 2020 RCV000162700.8
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
MSH6 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
5681 5715

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Aug 29, 2016)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal cancer type 5
Allele origin: unknown
Counsyl
Accession: SCV000489167.1
Submitted: (Nov 23, 2016)
Evidence details
Publications
PubMed (2)
Uncertain significance
(May 29, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000279483.9
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted MSH6 c.1144C>T at the cDNA level, p.His382Tyr (H382Y) at the protein level, and results in the change of a Histidine to … (more)
Likely benign
(Nov 16, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000213155.6
Submitted: (Nov 30, 2020)
Evidence details
Comment:
Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;In silico models in agreement (benign)
Uncertain significance
(Oct 21, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000551091.7
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces histidine with tyrosine at codon 382 of the MSH6 protein (p.His382Tyr). The histidine residue is weakly conserved and there is a … (more)
Uncertain significance
(Oct 06, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000690175.4
Submitted: (Jun 11, 2021)
Evidence details
Comment:
This missense variant replaces histidine with tyrosine at codon 382 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein structure … (more)
Uncertain significance
(May 19, 2021)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001432008.2
Submitted: (Jun 17, 2021)
Evidence details
Publications
PubMed (3)
Comment:
Variant summary: MSH6 c.1144C>T (p.His382Tyr) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign … (more)

Functional evidence

Help
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 this variant

Help
Title Author Journal Year Link
Germline Mutation in 1338 BRCA-Negative Chinese Hereditary Breast and/or Ovarian Cancer Patients: Clinical Testing with a Multigene Test Panel. Kwong A The Journal of molecular diagnostics : JMD 2020 PMID: 32068069
Prevalence of genetic susceptibility for breast and ovarian cancer in a non-cancer related study population: secondary germline findings from a Swiss single centre cohort. Kraemer D Swiss medical weekly 2019 PMID: 31422574
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Patterns and functional implications of rare germline variants across 12 cancer types. Lu C Nature communications 2015 PMID: 26689913
Classification of Amino Acid Substitutions in Mismatch Repair Proteins Using PON-MMR2. Niroula A Human mutation 2015 PMID: 26333163
LOVD v.2.0: the next generation in gene variant databases. Fokkema IF Human mutation 2011 PMID: 21520333

Text-mined citations for rs587779207...

Help
These 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 Nov 27, 2021