NM_000251.2(MSH2):c.2178G>C (p.Met726Ile) AND not specified

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 8, 2017
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:: RCV000486473.1

Allele description

NM_000251.2(MSH2):c.2178G>C (p.Met726Ile)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.2(MSH2):c.2178G>C (p.Met726Ile)

HGVS:

NC_000002.12:g.47476539G>C
NG_007110.2:g.78416G>C
NM_000251.2:c.2178G>C
NP_000242.1:p.Met726Ile
LRG_218t1:c.2178G>C
LRG_218:g.78416G>C
LRG_218p1:p.Met726Ile
NC_000002.11:g.47703678G>C
NM_000251.1:c.2178G>C
p.M726I

Protein change:

M726I

Links:

dbSNP: rs587782396

NCBI 1000 Genomes Browser:

rs587782396

Molecular consequence:

NM_000251.2:c.2178G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000565200	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Aug 12, 2016)	germline	clinical testing	Citation Link,
SCV000601459	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest pathogenicity assessment criteria)	Uncertain significance (Jun 8, 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

SCV000565200

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Aug 12, 2016)

germline

clinical testing

Citation Link,

SCV000601459

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest pathogenicity assessment criteria)

Uncertain significance
(Jun 8, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From GeneDx, SCV000565200.3

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

Description

This variant is denoted MSH2 c.2178G>C at the cDNA level, p.Met726Ile (M726I) at the protein level, and results in the change of a Methionine to an Isoleucine (ATG>ATC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Met726Ile was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Methionine and Isoleucine share similar properties, this is considered a conservative amino acid substitution. MSH2 Met726Ile occurs at a position that is conserved across species and is located within the ATPase domain (LÃ¼tzen 2008). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether MSH2 Met726Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000601459.1

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

Last Updated: Mar 31, 2019

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