NM_000179.3(MSH6):c.1190_1191del (p.Tyr397fs) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 9, 2023
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:: RCV000497288.12

Allele description [Variation Report for NM_000179.3(MSH6):c.1190_1191del (p.Tyr397fs)]

NM_000179.3(MSH6):c.1190_1191del (p.Tyr397fs)

Gene:

MSH6:mutS homolog 6 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.1190_1191del (p.Tyr397fs)

HGVS:

NC_000002.12:g.47799173_47799174del
NG_007111.1:g.21027_21028del
NM_000179.3:c.1190_1191delMANE SELECT
NM_001281492.2:c.800_801del
NM_001281493.2:c.284_285del
NM_001281494.2:c.284_285del
NP_000170.1:p.Tyr397fs
NP_001268421.1:p.Tyr267fs
NP_001268422.1:p.Tyr95fs
NP_001268423.1:p.Tyr95fs
LRG_219:g.21027_21028del
NC_000002.11:g.48026311_48026312del
NC_000002.11:g.48026312_48026313del
NM_000179.2:c.1190_1191delAT
p.Tyr397Cysfs*3
p.Y397CfsX3

Protein change:

Y267fs

Links:

dbSNP: rs63750439

NCBI 1000 Genomes Browser:

rs63750439

Molecular consequence:

NM_000179.3:c.1190_1191del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281492.2:c.800_801del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281493.2:c.284_285del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281494.2:c.284_285del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000211379	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 9, 2023)	germline	clinical testing	Citation Link,
SCV000691923	Mayo Clinic Laboratories, Mayo Clinic	no assertion criteria provided	Pathogenic	unknown	clinical testing
SCV001449662	Clinical Genetics and Genomics, Karolinska University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 14, 2017)	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

SCV000211379

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 9, 2023)

germline

clinical testing

Citation Link,

SCV000691923

Mayo Clinic Laboratories, Mayo Clinic

no assertion criteria provided

Pathogenic

unknown

clinical testing

SCV001449662

Clinical Genetics and Genomics, Karolinska University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 14, 2017)

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	3	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	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 GeneDx, SCV000211379.9

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals with early-onset colon cancer who had tumors showing microsatellite instability and/or loss of MSH6 on immunohistochemistry staining (Plaschke et al., 2004; Steinke et al., 2008; You et al., 2010; Yang et al., 2021); This variant is associated with the following publications: (PMID: 14974087, 32980694, 29922827, 18301448, 21081928, 26681312, 15483016, 36988593, 34178123)

#	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

From Mayo Clinic Laboratories, Mayo Clinic, SCV000691923.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics and Genomics, Karolinska University Hospital, SCV001449662.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	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	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

Last Updated: May 12, 2024

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