NM_000179.3(MSH6):c.938A>G (p.Lys313Arg) AND Lynch syndrome

delete

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 14, 2015
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:: RCV000206281.1

Allele description

NM_000179.3(MSH6):c.938A>G (p.Lys313Arg)

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.938A>G (p.Lys313Arg)

HGVS:

NC_000002.12:g.47798921A>G
NG_007111.1:g.20775A>G
NM_000179.3:c.938A>GMANE SELECT
NM_001281492.2:c.548A>G
NM_001281493.2:c.32A>G
NM_001281494.2:c.32A>G
NP_000170.1:p.Lys313Arg
NP_000170.1:p.Lys313Arg
NP_001268421.1:p.Lys183Arg
NP_001268422.1:p.Lys11Arg
NP_001268423.1:p.Lys11Arg
LRG_219t1:c.938A>G
LRG_219:g.20775A>G
LRG_219p1:p.Lys313Arg
NC_000002.11:g.48026060A>G
NM_000179.2:c.938A>G

Protein change:

K11R

Links:

dbSNP: rs753373644

NCBI 1000 Genomes Browser:

rs753373644

Molecular consequence:

NM_000179.3:c.938A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.548A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.32A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.32A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Lynch syndrome
Identifiers:: MONDO: MONDO:0005835; MedGen: C4552100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000261235	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 14, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000261235

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 14, 2015)

germline

clinical testing

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

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

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000261235.2

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

Description

This sequence change replaces lysine with arginine at codon 313 of the MSH6 protein (p.Lys313Arg). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature. 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this is a novel missense change that is not predicted to affect protein function or cause disease. However the evidence is insufficient at this time to prove that conclusively. 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: Dec 24, 2023

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