NM_000179.3(MSH6):c.469A>G (p.Lys157Glu) AND Hereditary nonpolyposis colorectal neoplasms

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 28, 2019
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:: RCV001045928.7

Allele description

NM_000179.3(MSH6):c.469A>G (p.Lys157Glu)

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.469A>G (p.Lys157Glu)

HGVS:

NC_000002.12:g.47795905A>G
NG_007111.1:g.17759A>G
NM_000179.3:c.469A>GMANE SELECT
NM_001281492.2:c.238-2706A>G
NM_001281493.2:c.-279-2706A>G
NM_001281494.2:c.-434A>G
NP_000170.1:p.Lys157Glu
LRG_219t1:c.469A>G
LRG_219:g.17759A>G
NC_000002.11:g.48023044A>G
NM_000179.2:c.469A>G

Protein change:

K157E

Links:

dbSNP: rs1572716094

NCBI 1000 Genomes Browser:

rs1572716094

Molecular consequence:

NM_001281494.2:c.-434A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001281492.2:c.238-2706A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001281493.2:c.-279-2706A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000179.3:c.469A>G - 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
SCV001209803	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 28, 2019)	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

SCV001209803

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 28, 2019)

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001209803.5

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. This variant has not been reported in the literature in individuals with MSH6-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 157 of the MSH6 protein (p.Lys157Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid.

#	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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