NM_000179.3(MSH6):c.49C>G (p.Leu17Val) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 26, 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:: RCV003863385.2

Allele description [Variation Report for NM_000179.3(MSH6):c.49C>G (p.Leu17Val)]

NM_000179.3(MSH6):c.49C>G (p.Leu17Val)

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.49C>G (p.Leu17Val)

HGVS:

NC_000002.12:g.47783282C>G
NG_007111.1:g.5136C>G
NG_166732.1:g.665C>G
NM_000179.3:c.49C>GMANE SELECT
NM_001281492.2:c.49C>G
NM_001281493.2:c.-688C>G
NM_001406795.1:c.49C>G
NM_001406796.1:c.49C>G
NM_001406797.1:c.-38+51C>G
NM_001406798.1:c.49C>G
NM_001406799.1:c.-280C>G
NM_001406800.1:c.49C>G
NM_001406801.1:c.-38+51C>G
NM_001406802.1:c.49C>G
NM_001406803.1:c.49C>G
NM_001406804.1:c.-7C>G
NM_001406805.1:c.-38+51C>G
NM_001406806.1:c.-69+51C>G
NM_001406807.1:c.-880C>G
NM_001406808.1:c.49C>G
NM_001406809.1:c.49C>G
NM_001406811.1:c.-688C>G
NM_001406812.1:c.-535C>G
NM_001406813.1:c.49C>G
NM_001406814.1:c.-946C>G
NM_001406815.1:c.-280+51C>G
NM_001406816.1:c.-491C>G
NM_001406817.1:c.49C>G
NM_001407362.1:c.49C>G
NP_000170.1:p.Leu17Val
NP_000170.1:p.Leu17Val
NP_001268421.1:p.Leu17Val
NP_001393724.1:p.Leu17Val
NP_001393725.1:p.Leu17Val
NP_001393727.1:p.Leu17Val
NP_001393729.1:p.Leu17Val
NP_001393731.1:p.Leu17Val
NP_001393732.1:p.Leu17Val
NP_001393737.1:p.Leu17Val
NP_001393738.1:p.Leu17Val
NP_001393742.1:p.Leu17Val
NP_001393746.1:p.Leu17Val
NP_001394291.1:p.Leu17Val
LRG_219t1:c.49C>G
LRG_219:g.5136C>G
LRG_219p1:p.Leu17Val
NC_000002.11:g.48010421C>G
NM_000179.2:c.49C>G
NR_176256.1:n.138C>G
NR_176257.1:n.138C>G
NR_176258.1:n.138C>G
NR_176259.1:n.138C>G
NR_176260.1:n.138C>G
NR_176261.1:n.138C>G

Protein change:

L17V

Molecular consequence:

NM_001281493.2:c.-688C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406799.1:c.-280C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406804.1:c.-7C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406807.1:c.-880C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406811.1:c.-688C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406812.1:c.-535C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406814.1:c.-946C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406816.1:c.-491C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001406797.1:c.-38+51C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001406801.1:c.-38+51C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001406805.1:c.-38+51C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001406806.1:c.-69+51C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001406815.1:c.-280+51C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000179.3:c.49C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.49C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406795.1:c.49C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406796.1:c.49C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406798.1:c.49C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406800.1:c.49C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406802.1:c.49C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406803.1:c.49C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406808.1:c.49C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406809.1:c.49C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406813.1:c.49C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001406817.1:c.49C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407362.1:c.49C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_176256.1:n.138C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176257.1:n.138C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176258.1:n.138C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176259.1:n.138C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176261.1:n.138C>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
SCV004666863	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 26, 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

SCV004666863

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 26, 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, SCV004666863.1

#	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 17 of the MSH6 protein (p.Leu17Val).

#	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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