NM_000179.3(MSH6):c.3185G>A (p.Cys1062Tyr) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 7, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002325458.2

Allele description [Variation Report for NM_000179.3(MSH6):c.3185G>A (p.Cys1062Tyr)]

NM_000179.3(MSH6):c.3185G>A (p.Cys1062Tyr)

Gene:

MSH6:mutS homolog 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.3185G>A (p.Cys1062Tyr)

HGVS:

NC_000002.12:g.47803432G>A
NG_007111.1:g.25286G>A
NM_000179.3:c.3185G>AMANE SELECT
NM_001281492.2:c.2795G>A
NM_001281493.2:c.2279G>A
NM_001281494.2:c.2279G>A
NP_000170.1:p.Cys1062Tyr
NP_000170.1:p.Cys1062Tyr
NP_001268421.1:p.Cys932Tyr
NP_001268422.1:p.Cys760Tyr
NP_001268423.1:p.Cys760Tyr
LRG_219t1:c.3185G>A
LRG_219:g.25286G>A
LRG_219p1:p.Cys1062Tyr
NC_000002.11:g.48030571G>A
NM_000179.2:c.3185G>A

Protein change:

C1062Y

Links:

dbSNP: rs1558386797

NCBI 1000 Genomes Browser:

rs1558386797

Molecular consequence:

NM_000179.3:c.3185G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.2795G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.2279G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.2279G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002609228	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Apr 7, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002609228

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Apr 7, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Using Somatic Mutations from Tumors to Classify Variants in Mismatch Repair Genes.

Shirts BH, Konnick EQ, Upham S, Walsh T, Ranola JMO, Jacobson AL, King MC, Pearlman R, Hampel H, Pritchard CC.

Am J Hum Genet. 2018 Jul 5;103(1):19-29. doi: 10.1016/j.ajhg.2018.05.001. Epub 2018 Jun 7.

PubMed [citation]

PMID:: 29887214
PMCID:: PMC6035155

Details of each submission

From Ambry Genetics, SCV002609228.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The p.C1062Y variant (also known as c.3185G>A), located in coding exon 5 of the MSH6 gene, results from a G to A substitution at nucleotide position 3185. The cysteine at codon 1062 is replaced by tyrosine, an amino acid with highly dissimilar properties. Using a Bayesian analysis that incorporates tumor mutation data, this variant was classified as likely pathogenic (Shirts BH et al. Am J Hum Genet, 2018 07;103:19-29). This amino acid position is not well conserved in available vertebrate species. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

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