NM_000179.3(MSH6):c.2275C>G (p.Leu759Val) AND Lynch syndrome 5

Germline classification:: Uncertain significance (1 submission)
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:: RCV003388603.2

Allele description [Variation Report for NM_000179.3(MSH6):c.2275C>G (p.Leu759Val)]

NM_000179.3(MSH6):c.2275C>G (p.Leu759Val)

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.2275C>G (p.Leu759Val)

HGVS:

NC_000002.12:g.47800258C>G
NG_007111.1:g.22112C>G
NM_000179.3:c.2275C>GMANE SELECT
NM_001281492.2:c.1885C>G
NM_001281493.2:c.1369C>G
NM_001281494.2:c.1369C>G
NP_000170.1:p.Leu759Val
NP_001268421.1:p.Leu629Val
NP_001268422.1:p.Leu457Val
NP_001268423.1:p.Leu457Val
LRG_219t1:c.2275C>G
LRG_219:g.22112C>G
NC_000002.11:g.48027397C>G
NM_000179.2:c.2275C>G

Protein change:

L457V

Links:

dbSNP: rs1669442548

NCBI 1000 Genomes Browser:

rs1669442548

Molecular consequence:

NM_000179.3:c.2275C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.1885C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.1369C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.1369C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Lynch syndrome 5 (LYNCH5)
Synonyms:: Colorectal cancer, hereditary nonpolyposis, type 5; Hereditary non-polyposis colorectal cancer, type 5
Identifiers:: MONDO: MONDO:0013710; MedGen: C1833477; Orphanet: 144; OMIM: 614350

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004100451	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	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

SCV004100451

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV004100451.1

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

Description

The missense variant p.L759V in MSH6 (NM_000179.3) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. It has been submitted to ClinVar as Uncertain Significance but there are no details for independent assessment. The p.L759V variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a small physicochemical difference between leucine and valine, which is not likely to impact secondary protein structure as these residues share similar properties. For these reasons, this variant has been classified as Uncertain Significance

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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