NM_000251.3(MSH2):c.2087C>T (p.Pro696Leu) AND Lynch syndrome 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 7, 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:: RCV003452886.1

Allele description [Variation Report for NM_000251.3(MSH2):c.2087C>T (p.Pro696Leu)]

NM_000251.3(MSH2):c.2087C>T (p.Pro696Leu)

Gene:

MSH2:mutS homolog 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.2087C>T (p.Pro696Leu)

HGVS:

NC_000002.12:g.47476448C>T
NG_007110.2:g.78325C>T
NM_000251.3:c.2087C>TMANE SELECT
NM_001258281.1:c.1889C>T
NP_000242.1:p.Pro696Leu
NP_000242.1:p.Pro696Leu
NP_001245210.1:p.Pro630Leu
LRG_218t1:c.2087C>T
LRG_218:g.78325C>T
LRG_218p1:p.Pro696Leu
NC_000002.11:g.47703587C>T
NM_000251.1:c.2087C>T
NM_000251.2:c.2087C>T
P43246:p.Pro696Leu

Protein change:

P630L

Links:

UniProtKB: P43246#VAR_054519; dbSNP: rs267607994

NCBI 1000 Genomes Browser:

rs267607994

Molecular consequence:

NM_000251.3:c.2087C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258281.1:c.1889C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Lynch syndrome 1
Synonyms:: COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 1; MSH2-Related Hereditary Non-Polyposis Colon Cancer; Lynch syndrome I; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007356; MedGen: C2936783; Orphanet: 144; OMIM: 120435

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004186721	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (Aug 7, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27629256, 26951660 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004186721

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Likely pathogenic
(Aug 7, 2023)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Assessment of the InSiGHT Interpretation Criteria for the Clinical Classification of 24 MLH1 and MSH2 Gene Variants.

Tricarico R, Kasela M, Mareni C, Thompson BA, Drouet A, Staderini L, Gorelli G, Crucianelli F, Ingrosso V, Kantelinen J, Papi L, De Angioletti M, Berardi M, Gaildrat P, Soukarieh O, Turchetti D, Martins A, Spurdle AB, Nyström M, Genuardi M; InSiGHT Variant Interpretation Committee..

Hum Mutat. 2017 Jan;38(1):64-77. doi: 10.1002/humu.23117. Epub 2016 Oct 17.

PubMed [citation]

PMID:: 27629256

Oligonucleotide-directed mutagenesis screen to identify pathogenic Lynch syndrome-associated MSH2 DNA mismatch repair gene variants.

Houlleberghs H, Dekker M, Lantermans H, Kleinendorst R, Dubbink HJ, Hofstra RM, Verhoef S, Te Riele H.

Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):4128-33. doi: 10.1073/pnas.1520813113. Epub 2016 Mar 7.

PubMed [citation]

PMID:: 26951660
PMCID:: PMC4839441

Details of each submission

From Myriad Genetics, Inc., SCV004186721.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is considered likely pathogenic. Functional studies indicate this variant impacts protein function [PMID: 27629256, 26951660]. This variant is expected to disrupt protein structure [Myriad internal data].

#	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

Last Updated: Sep 29, 2024

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