NM_000179.3(MSH6):c.3649A>G (p.Arg1217Gly) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 5, 2023
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:: RCV000122965.11

Allele description [Variation Report for NM_000179.3(MSH6):c.3649A>G (p.Arg1217Gly)]

NM_000179.3(MSH6):c.3649A>G (p.Arg1217Gly)

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.3649A>G (p.Arg1217Gly)

HGVS:

NC_000002.12:g.47806206A>G
NG_007111.1:g.28060A>G
NG_008397.1:g.104470T>C
NM_000179.3:c.3649A>GMANE SELECT
NM_001281492.2:c.3259A>G
NM_001281493.2:c.2743A>G
NM_001281494.2:c.2743A>G
NP_000170.1:p.Arg1217Gly
NP_000170.1:p.Arg1217Gly
NP_001268421.1:p.Arg1087Gly
NP_001268422.1:p.Arg915Gly
NP_001268423.1:p.Arg915Gly
LRG_219t1:c.3649A>G
LRG_219:g.28060A>G
LRG_219p1:p.Arg1217Gly
NC_000002.11:g.48033345A>G
NM_000179.2:c.3649A>G

Protein change:

R1087G

Links:

dbSNP: rs587780677

NCBI 1000 Genomes Browser:

rs587780677

Molecular consequence:

NM_000179.3:c.3649A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.3259A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.2743A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.2743A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Thioflavicoccus mobilis 8321
Thioflavicoccus mobilis 8321
Thioflavicoccus mobilis 8321 genome sequencing project

BioProject
LOC107475320 [Arachis duranensis]
LOC107475320 [Arachis duranensis]
Gene ID:107475320

Gene
LOC130963691 [Arachis stenosperma]
LOC130963691 [Arachis stenosperma]
Gene ID:130963691

Gene
LOC112728026 [Arachis hypogaea]
LOC112728026 [Arachis hypogaea]
Gene ID:112728026

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000166232	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 5, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24556621, 27978560, 29333623, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000166232

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 5, 2023)

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

Frequent germline deleterious mutations in DNA repair genes in familial prostate cancer cases are associated with advanced disease.

Leongamornlert D, Saunders E, Dadaev T, Tymrakiewicz M, Goh C, Jugurnauth-Little S, Kozarewa I, Fenwick K, Assiotis I, Barrowdale D, Govindasami K, Guy M, Sawyer E, Wilkinson R; UKGPCS Collaborators., Antoniou AC, Eeles R, Kote-Jarai Z.

Br J Cancer. 2014 Mar 18;110(6):1663-72. doi: 10.1038/bjc.2014.30. Epub 2014 Feb 20.

PubMed [citation]

PMID:: 24556621
PMCID:: PMC3960610

Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer.

Pearlman R, Frankel WL, Swanson B, Zhao W, Yilmaz A, Miller K, Bacher J, Bigley C, Nelsen L, Goodfellow PJ, Goldberg RM, Paskett E, Shields PG, Freudenheim JL, Stanich PP, Lattimer I, Arnold M, Liyanarachchi S, Kalady M, Heald B, Greenwood C, Paquette I, et al.

JAMA Oncol. 2017 Apr 1;3(4):464-471. doi: 10.1001/jamaoncol.2016.5194.

PubMed [citation]

PMID:: 27978560
PMCID:: PMC5564179

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000166232.10

#	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 arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1217 of the MSH6 protein (p.Arg1217Gly). This variant is present in population databases (rs587780677, gnomAD 0.007%). This missense change has been observed in individual(s) with colorectal cancer, prostate cancer, and sebaceous neoplasm (PMID: 24556621, 27978560, 29333623). ClinVar contains an entry for this variant (Variation ID: 135842). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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: Sep 29, 2024

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