NM_000179.3(MSH6):c.719G>T (p.Arg240Leu) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 1, 2021
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:: RCV001901318.6

Allele description [Variation Report for NM_000179.3(MSH6):c.719G>T (p.Arg240Leu)]

NM_000179.3(MSH6):c.719G>T (p.Arg240Leu)

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.719G>T (p.Arg240Leu)

HGVS:

NC_000002.12:g.47798702G>T
NG_007111.1:g.20556G>T
NM_000179.3:c.719G>TMANE SELECT
NM_001281492.2:c.329G>T
NM_001281493.2:c.-188G>T
NM_001281494.2:c.-188G>T
NP_000170.1:p.Arg240Leu
NP_001268421.1:p.Arg110Leu
LRG_219:g.20556G>T
NC_000002.11:g.48025841G>T

Protein change:

R110L

Links:

dbSNP: rs542848931

NCBI 1000 Genomes Browser:

rs542848931

Molecular consequence:

NM_001281493.2:c.-188G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001281494.2:c.-188G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000179.3:c.719G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.329G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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Megalaria phayapipakiana RAMK Kalb 41762 ITS region; from TYPE material
Megalaria phayapipakiana RAMK Kalb 41762 ITS region; from TYPE material
gi|2366254061|ref|NR_182746.1|

Nucleotide
Homo sapiens LOC122258 (LOC122258), mRNA
Homo sapiens LOC122258 (LOC122258), mRNA
gi|21687031|ref|NM_145248.1|

Nucleotide
AAB00103 (0)
PMC
Megalaria crispisulcans voucher UNITEC 12902 internal transcribed spacer 1, part...
Megalaria crispisulcans voucher UNITEC 12902 internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene, complete sequence; and internal transcribed spacer 2, partial sequence
gi|2579630618|gb|OR575320.1|

Nucleotide
N,N'-bis(2-1(piperidino)-ethyl)-3,4,9,10-perylene-tetracarboxylic diimide [Suppl...
N,N'-bis(2-1(piperidino)-ethyl)-3,4,9,10-perylene-tetracarboxylic diimide [Supplementary Concept]
structure in first source<br/>Date introduced: December 22, 1998<br/>

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002168387	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 1, 2021)	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

SCV002168387

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 1, 2021)

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, SCV002168387.3

#	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 arginine with leucine at codon 240 of the MSH6 protein (p.Arg240Leu). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. 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. 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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