NM_000179.3(MSH6):c.38A>C (p.Lys13Thr) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 31, 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:: RCV000627725.10

Allele description [Variation Report for NM_000179.3(MSH6):c.38A>C (p.Lys13Thr)]

NM_000179.3(MSH6):c.38A>C (p.Lys13Thr)

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.38A>C (p.Lys13Thr)

Other names:

p.K13T:AAG>ACG

HGVS:

NC_000002.12:g.47783271A>C
NG_007111.1:g.5125A>C
NM_000179.3:c.38A>CMANE SELECT
NM_001281492.2:c.38A>C
NM_001281493.2:c.-699A>C
NP_000170.1:p.Lys13Thr
NP_000170.1:p.Lys13Thr
NP_001268421.1:p.Lys13Thr
LRG_219t1:c.38A>C
LRG_219:g.5125A>C
LRG_219p1:p.Lys13Thr
NC_000002.11:g.48010410A>C
NM_000179.2:c.38A>C
P52701:p.Lys13Thr

Protein change:

K13T

Links:

UniProtKB: P52701#VAR_038032; dbSNP: rs41294988

NCBI 1000 Genomes Browser:

rs41294988

Molecular consequence:

NM_001281493.2:c.-699A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000179.3:c.38A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.38A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000551144	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18033691, 23621914, 31965077, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000551144

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancer.

Barnetson RA, Cartwright N, van Vliet A, Haq N, Drew K, Farrington S, Williams N, Warner J, Campbell H, Porteous ME, Dunlop MG.

Hum Mutat. 2008 Mar;29(3):367-74.

PubMed [citation]

PMID:: 18033691

CoDP: predicting the impact of unclassified genetic variants in MSH6 by the combination of different properties of the protein.

Terui H, Akagi K, Kawame H, Yura K.

J Biomed Sci. 2013 Apr 28;20:25. doi: 10.1186/1423-0127-20-25.

PubMed [citation]

PMID:: 23621914
PMCID:: PMC3651391

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000551144.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 13 of the MSH6 protein (p.Lys13Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with colorectal cancer (PMID: 18033691). ClinVar contains an entry for this variant (Variation ID: 36596). An algorithm developed specifically for the MSH6 gene suggests that this missense change is likely to be tolerated (PMID: 23621914). Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on MSH6 function (PMID: 31965077). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Oct 8, 2024

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