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NM_000179.3(MSH6):c.3536C>A (p.Ala1179Asp) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 24, 2017
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:
RCV000630087.6

Allele description

NM_000179.3(MSH6):c.3536C>A (p.Ala1179Asp)

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.3536C>A (p.Ala1179Asp)
HGVS:
  • NC_000002.12:g.47805007C>A
  • NG_007111.1:g.26861C>A
  • NG_008397.1:g.105669G>T
  • NM_000179.3:c.3536C>AMANE SELECT
  • NM_001281492.2:c.3146C>A
  • NM_001281493.2:c.2630C>A
  • NM_001281494.2:c.2630C>A
  • NP_000170.1:p.Ala1179Asp
  • NP_000170.1:p.Ala1179Asp
  • NP_001268421.1:p.Ala1049Asp
  • NP_001268422.1:p.Ala877Asp
  • NP_001268423.1:p.Ala877Asp
  • LRG_219t1:c.3536C>A
  • LRG_219:g.26861C>A
  • LRG_219p1:p.Ala1179Asp
  • NC_000002.11:g.48032146C>A
  • NM_000179.2:c.3536C>A
Protein change:
A1049D
Links:
dbSNP: rs773583312
NCBI 1000 Genomes Browser:
rs773583312
Molecular consequence:
  • NM_000179.3:c.3536C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281492.2:c.3146C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281493.2:c.2630C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281494.2:c.2630C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary nonpolyposis colorectal neoplasms
Identifiers:
MeSH: D003123; MedGen: C0009405

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000751043Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Aug 24, 2017) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000751043.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This variant is present in population databases (rs773583312, ExAC 0.009%) but has not been reported in the literature in individuals with a MSH6-related disease. This sequence change replaces alanine with aspartic acid at codon 1179 of the MSH6 protein (p.Ala1179Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 7, 2024