NM_002439.5(MSH3):c.2179C>T (p.Arg727Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 22, 2024
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:: RCV000817435.7

Allele description [Variation Report for NM_002439.5(MSH3):c.2179C>T (p.Arg727Ter)]

NM_002439.5(MSH3):c.2179C>T (p.Arg727Ter)

Gene:

MSH3:mutS homolog 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q14.1

Genomic location:

Preferred name:

NM_002439.5(MSH3):c.2179C>T (p.Arg727Ter)

HGVS:

NC_000005.10:g.80768929C>T
NG_016607.2:g.119455C>T
NM_002439.5:c.2179C>TMANE SELECT
NP_002430.3:p.Arg727Ter
NC_000005.9:g.80064748C>T
NG_016607.1:g.119455C>T
NM_002439.3:c.2179C>T
NM_002439.4:c.2179C>T

Protein change:

R727*

Links:

dbSNP: rs376667075

NCBI 1000 Genomes Browser:

rs376667075

Molecular consequence:

NM_002439.5:c.2179C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000957995	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 22, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27476653, 37402566, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000957995

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 22, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Exome Sequencing Identifies Biallelic MSH3 Germline Mutations as a Recessive Subtype of Colorectal Adenomatous Polyposis.

Adam R, Spier I, Zhao B, Kloth M, Marquez J, Hinrichsen I, Kirfel J, Tafazzoli A, Horpaopan S, Uhlhaas S, Stienen D, Friedrichs N, Altmüller J, Laner A, Holzapfel S, Peters S, Kayser K, Thiele H, Holinski-Feder E, Marra G, Kristiansen G, Nöthen MM, et al.

Am J Hum Genet. 2016 Aug 4;99(2):337-51. doi: 10.1016/j.ajhg.2016.06.015. Epub 2016 Jul 28.

PubMed [citation]

PMID:: 27476653
PMCID:: PMC4974087

MSH3: a confirmed predisposing gene for adenomatous polyposis.

Villy MC, Masliah-Planchon J, Schnitzler A, Delhomelle H, Buecher B, Filser M, Merchadou K, Golmard L, Melaabi S, Vacher S, Blanluet M, Suybeng V, Corsini C, Dhooge M, Hamzaoui N, Farelly S, Ait Omar A, Benamouzig R, Caumette V, Bahuau M, Cucherousset J, Allory Y, et al.

J Med Genet. 2023 Nov 27;60(12):1198-1205. doi: 10.1136/jmg-2023-109341.

PubMed [citation]

PMID:: 37402566

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000957995.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Arg727*) in the MSH3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH3 are known to be pathogenic (PMID: 27476653, 37402566). This variant is present in population databases (rs376667075, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 660274). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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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