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NM_000251.3(MSH2):c.1270C>T (p.His424Tyr)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
4 (Most recent: Nov 30, 2020)
Last evaluated:
Apr 25, 2019
Accession:
VCV000142169.7
Variation ID:
142169
Description:
single nucleotide variant
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NM_000251.3(MSH2):c.1270C>T (p.His424Tyr)

Allele ID
151883
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2p21
Genomic location
2: 47429935 (GRCh38) GRCh38 UCSC
2: 47657074 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_218t1:c.1270C>T LRG_218p1:p.His424Tyr
LRG_218:g.31812C>T
NM_000251.2:c.1270C>T NP_000242.1:p.His424Tyr missense
... more HGVS
Protein change
H424Y, H358Y
Other names
-
Canonical SPDI
NC_000002.12:47429934:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00001
Links
ClinGen: CA017712
dbSNP: rs587782278
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Apr 25, 2019 RCV000464371.3
Uncertain significance 1 criteria provided, single submitter May 23, 2018 RCV000481281.2
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Mar 26, 2019 RCV000131137.7
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
MSH2 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
4521 4606

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Dec 06, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000186072.6
Submitted: (Nov 30, 2020)
Evidence details
Comment:
In silico models in agreement (benign);Other strong data supporting benign classification
Uncertain significance
(May 23, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000565728.4
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted MSH2 c.1270C>T at the cDNA level, p.His424Tyr (H424Y) at the protein level, and results in the change of a Histidine to … (more)
Uncertain significance
(Apr 25, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colon cancer
Allele origin: germline
Invitae
Accession: SCV000548214.4
Submitted: (Feb 06, 2020)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change replaces histidine with tyrosine at codon 424 of the MSH2 protein (p.His424Tyr). The histidine residue is weakly conserved and there is a … (more)
Uncertain significance
(Mar 26, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000689968.3
Submitted: (May 19, 2020)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer. Pal T British journal of cancer 2012 PMID: 23047549

Text-mined citations for rs587782278...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021