NM_000179.3(MSH6):c.708A>C (p.Gln236His) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 15, 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:: RCV001051535.7

Allele description [Variation Report for NM_000179.3(MSH6):c.708A>C (p.Gln236His)]

NM_000179.3(MSH6):c.708A>C (p.Gln236His)

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.708A>C (p.Gln236His)

HGVS:

NC_000002.12:g.47798691A>C
NG_007111.1:g.20545A>C
NM_000179.3:c.708A>CMANE SELECT
NM_001281492.2:c.318A>C
NM_001281493.2:c.-199A>C
NM_001281494.2:c.-199A>C
NP_000170.1:p.Gln236His
NP_001268421.1:p.Gln106His
LRG_219t1:c.708A>C
LRG_219:g.20545A>C
NC_000002.11:g.48025830A>C
NM_000179.2:c.708A>C

Protein change:

Q106H

Links:

dbSNP: rs1322117538

NCBI 1000 Genomes Browser:

rs1322117538

Molecular consequence:

NM_001281493.2:c.-199A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001281494.2:c.-199A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000179.3:c.708A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.318A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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ATP synthase F0 subunit 8 (mitochondrion) [Tettigades major]
ATP synthase F0 subunit 8 (mitochondrion) [Tettigades major]
gi|1406949507|gb|AWV84410.1|

Protein
PREDICTED: Solanum lycopersicum uncharacterized LOC101244920 (LOC101244920), mRN...
PREDICTED: Solanum lycopersicum uncharacterized LOC101244920 (LOC101244920), mRNA
gi|1444438577|ref|XM_004249667.4|

Nucleotide
Ezohelix gainesi mitochondrial DNA, external transcribed spacer, partial sequenc...
Ezohelix gainesi mitochondrial DNA, external transcribed spacer, partial sequence, isolate: dna_no_315
gi|1112916538|dbj|LC168994.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001215692	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 15, 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

SCV001215692

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 15, 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, SCV001215692.5

#	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. ClinVar contains an entry for this variant (Variation ID: 847895). 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 histidine, which is basic and polar, at codon 236 of the MSH6 protein (p.Gln236His).

#	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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