NM_000179.3(MSH6):c.974A>G (p.Gln325Arg) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 29, 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:: RCV003760283.2

Allele description [Variation Report for NM_000179.3(MSH6):c.974A>G (p.Gln325Arg)]

NM_000179.3(MSH6):c.974A>G (p.Gln325Arg)

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.974A>G (p.Gln325Arg)

HGVS:

NC_000002.12:g.47798957A>G
NG_007111.1:g.20811A>G
NM_000179.3:c.974A>GMANE SELECT
NM_001281492.2:c.584A>G
NM_001281493.2:c.68A>G
NM_001281494.2:c.68A>G
NM_001406795.1:c.1070A>G
NM_001406796.1:c.974A>G
NM_001406797.1:c.677A>G
NM_001406798.1:c.974A>G
NM_001406799.1:c.449A>G
NM_001406800.1:c.974A>G
NM_001406801.1:c.677A>G
NM_001406802.1:c.1070A>G
NM_001406803.1:c.974A>G
NM_001406804.1:c.896A>G
NM_001406805.1:c.677A>G
NM_001406806.1:c.449A>G
NM_001406807.1:c.449A>G
NM_001406808.1:c.974A>G
NM_001406809.1:c.974A>G
NM_001406811.1:c.68A>G
NM_001406812.1:c.68A>G
NM_001406813.1:c.980A>G
NM_001406814.1:c.68A>G
NM_001406815.1:c.68A>G
NM_001406816.1:c.68A>G
NM_001406817.1:c.974A>G
NM_001406818.1:c.677A>G
NM_001406819.1:c.677A>G
NM_001406820.1:c.677A>G
NM_001406821.1:c.677A>G
NM_001406822.1:c.677A>G
NM_001406823.1:c.68A>G
NM_001406824.1:c.677A>G
NM_001406825.1:c.677A>G
NM_001406826.1:c.806A>G
NM_001406827.1:c.677A>G
NM_001406828.1:c.677A>G
NM_001406829.1:c.68A>G
NM_001406830.1:c.677A>G
NM_001407362.1:c.628-1709A>G
NP_000170.1:p.Gln325Arg
NP_000170.1:p.Gln325Arg
NP_001268421.1:p.Gln195Arg
NP_001268422.1:p.Gln23Arg
NP_001268423.1:p.Gln23Arg
NP_001393724.1:p.Gln357Arg
NP_001393725.1:p.Gln325Arg
NP_001393726.1:p.Gln226Arg
NP_001393727.1:p.Gln325Arg
NP_001393728.1:p.Gln150Arg
NP_001393729.1:p.Gln325Arg
NP_001393730.1:p.Gln226Arg
NP_001393731.1:p.Gln357Arg
NP_001393732.1:p.Gln325Arg
NP_001393733.1:p.Gln299Arg
NP_001393734.1:p.Gln226Arg
NP_001393735.1:p.Gln150Arg
NP_001393736.1:p.Gln150Arg
NP_001393737.1:p.Gln325Arg
NP_001393738.1:p.Gln325Arg
NP_001393740.1:p.Gln23Arg
NP_001393741.1:p.Gln23Arg
NP_001393742.1:p.Gln327Arg
NP_001393743.1:p.Gln23Arg
NP_001393744.1:p.Gln23Arg
NP_001393745.1:p.Gln23Arg
NP_001393746.1:p.Gln325Arg
NP_001393747.1:p.Gln226Arg
NP_001393748.1:p.Gln226Arg
NP_001393749.1:p.Gln226Arg
NP_001393750.1:p.Gln226Arg
NP_001393751.1:p.Gln226Arg
NP_001393752.1:p.Gln23Arg
NP_001393753.1:p.Gln226Arg
NP_001393754.1:p.Gln226Arg
NP_001393755.1:p.Gln269Arg
NP_001393756.1:p.Gln226Arg
NP_001393757.1:p.Gln226Arg
NP_001393758.1:p.Gln23Arg
NP_001393759.1:p.Gln226Arg
LRG_219t1:c.974A>G
LRG_219:g.20811A>G
LRG_219p1:p.Gln325Arg
NC_000002.11:g.48026096A>G
NM_000179.2:c.974A>G
NR_176257.1:n.1063A>G
NR_176258.1:n.1063A>G
NR_176259.1:n.1063A>G
NR_176261.1:n.1063A>G

Protein change:

Q150R

Molecular consequence:

NM_001407362.1:c.628-1709A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000179.3:c.974A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.584A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.68A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.68A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406795.1:c.1070A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406796.1:c.974A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406797.1:c.677A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406798.1:c.974A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406799.1:c.449A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406800.1:c.974A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406801.1:c.677A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406802.1:c.1070A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406803.1:c.974A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406804.1:c.896A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406805.1:c.677A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406806.1:c.449A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406807.1:c.449A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406808.1:c.974A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406809.1:c.974A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406811.1:c.68A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406812.1:c.68A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406813.1:c.980A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406814.1:c.68A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406815.1:c.68A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406816.1:c.68A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406817.1:c.974A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406818.1:c.677A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406819.1:c.677A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406820.1:c.677A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406821.1:c.677A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406822.1:c.677A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406823.1:c.68A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406824.1:c.677A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406825.1:c.677A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406826.1:c.806A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406827.1:c.677A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406828.1:c.677A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406829.1:c.68A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406830.1:c.677A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_176257.1:n.1063A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176258.1:n.1063A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176259.1:n.1063A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176261.1:n.1063A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV004523554	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 29, 2022)	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

SCV004523554

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 29, 2022)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004523554.1

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

Description

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MSH6 protein function. This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 325 of the MSH6 protein (p.Gln325Arg).

#	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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