NM_000179.3(MSH6):c.1186C>G (p.Leu396Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Benign (5 submissions)
Last evaluated:: Sep 27, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000157762.12

Allele description [Variation Report for NM_000179.3(MSH6):c.1186C>G (p.Leu396Val)]

NM_000179.3(MSH6):c.1186C>G (p.Leu396Val)

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.1186C>G (p.Leu396Val)

Other names:

p.L396V:CTC>GTC

HGVS:

NC_000002.12:g.47799169C>G
NG_007111.1:g.21023C>G
NM_000179.3:c.1186C>GMANE SELECT
NM_001281492.2:c.796C>G
NM_001281493.2:c.280C>G
NM_001281494.2:c.280C>G
NP_000170.1:p.Leu396Val
NP_000170.1:p.Leu396Val
NP_001268421.1:p.Leu266Val
NP_001268422.1:p.Leu94Val
NP_001268423.1:p.Leu94Val
LRG_219t1:c.1186C>G
LRG_219:g.21023C>G
LRG_219p1:p.Leu396Val
NC_000002.11:g.48026308C>G
NM_000179.2:c.1186C>G
P52701:p.Leu396Val
p.L396V

Protein change:

L266V

Links:

UniProtKB: P52701#VAR_012958; dbSNP: rs2020908

NCBI 1000 Genomes Browser:

rs2020908

Molecular consequence:

NM_000179.3:c.1186C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.796C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.280C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.280C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000212712	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Benign (Aug 20, 2014)	germline	clinical testing	Citation Link,
SCV000267054	Vantari Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Dec 3, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000537391	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jan 1, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000788042	True Health Diagnostics	no assertion criteria provided	Benign (Feb 20, 2018)	germline	clinical testing
SCV002819191	Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Sep 27, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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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

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 Ambry Genetics, SCV000212712.7

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

Description

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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

From Vantari Genetics, SCV000267054.1

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

#	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

From Color Diagnostics, LLC DBA Color Health, SCV000537391.2

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

#	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

From True Health Diagnostics, SCV000788042.1

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

#	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

From Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C., SCV002819191.1

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

#	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: Jun 9, 2024

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