NM_000179.3(MSH6):c.19C>A (p.Leu7Met) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 18, 2019
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:: RCV001194398.5

Allele description [Variation Report for NM_000179.3(MSH6):c.19C>A (p.Leu7Met)]

NM_000179.3(MSH6):c.19C>A (p.Leu7Met)

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.19C>A (p.Leu7Met)

HGVS:

NC_000002.12:g.47783252C>A
NG_007111.1:g.5106C>A
NM_000179.3:c.19C>AMANE SELECT
NM_001281492.2:c.19C>A
NM_001281493.2:c.-718C>A
NP_000170.1:p.Leu7Met
NP_000170.1:p.Leu7Met
NP_001268421.1:p.Leu7Met
LRG_219t1:c.19C>A
LRG_219:g.5106C>A
LRG_219p1:p.Leu7Met
NC_000002.11:g.48010391C>A
NM_000179.2:c.19C>A

Protein change:

L7M

Links:

dbSNP: rs1064795094

NCBI 1000 Genomes Browser:

rs1064795094

Molecular consequence:

NM_001281493.2:c.-718C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000179.3:c.19C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.19C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Mus musculus spermatid maturation 1 (Spem1), mRNA
Mus musculus spermatid maturation 1 (Spem1), mRNA
gi|144227236|ref|NM_028855.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001363909	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Oct 24, 2019)	germline	clinical testing	Citation Link,
SCV002067798	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 18, 2019)	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

SCV001363909

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Oct 24, 2019)

germline

clinical testing

Citation Link,

SCV002067798

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 18, 2019)

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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001363909.1

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

Description

Variant summary: MSH6 c.19C>A (p.Leu7Met) results in a conservative amino acid change located in the PCNA-binding motif (Kariola 2002) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 245242 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.19C>A in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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

From Genetic Services Laboratory, University of Chicago, SCV002067798.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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