NM_002439.5(MSH3):c.2876_2877del (p.Thr959fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 12, 2023
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:: RCV000813391.6

Allele description [Variation Report for NM_002439.5(MSH3):c.2876_2877del (p.Thr959fs)]

NM_002439.5(MSH3):c.2876_2877del (p.Thr959fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

5q14.1

Genomic location:

Preferred name:

NM_002439.5(MSH3):c.2876_2877del (p.Thr959fs)

HGVS:

NC_000005.10:g.80854190CA[1]
NC_000005.9:g.80150008_80150009del
NG_016607.2:g.204716CA[1]
NM_002439.5:c.2876_2877delMANE SELECT
NP_002430.3:p.Thr959fs
NC_000005.9:g.80150008_80150009del
NC_000005.9:g.80150008_80150009delAC
NC_000005.9:g.80150009CA[1]
NM_002439.3:c.2876_2877delCA
NM_002439.4:c.2876_2877del
NM_002439.4:c.2876_2877delCA

Protein change:

T959fs

Links:

dbSNP: rs1580091512

NCBI 1000 Genomes Browser:

rs1580091512

Molecular consequence:

NM_002439.5:c.2876_2877del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000953750	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 12, 2023)	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

SCV000953750

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 12, 2023)

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 Invitae, SCV000953750.6

#	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.Thr959Serfs*17) 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 not present in population databases (gnomAD no frequency). 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: 656877). 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: Feb 20, 2024

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