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NM_000535.7(PMS2):c.1361T>C (p.Leu454Pro)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
3 (Most recent: Jan 7, 2021)
Last evaluated:
Feb 26, 2020
Accession:
VCV000411076.6
Variation ID:
411076
Description:
single nucleotide variant
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NM_000535.7(PMS2):c.1361T>C (p.Leu454Pro)

Allele ID
396364
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
7p22.1
Genomic location
7: 5987404 (GRCh38) GRCh38 UCSC
7: 6027035 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_161:g.26703T>C
LRG_161t1:c.1361T>C
NC_000007.13:g.6027035A>G
... more HGVS
Protein change
L454P, L143P, L263P, L348P, L351P, L402P, L319P, L267P
Other names
-
Canonical SPDI
NC_000007.14:5987403:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00002
The Genome Aggregation Database (gnomAD) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00004
Links
ClinGen: CA043156
dbSNP: rs772659239
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 Feb 26, 2020 RCV000472222.3
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Jan 7, 2020 RCV000574931.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
PMS2 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
3086 3151

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Apr 23, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000663428.3
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (1)
Comment:
In silico models in agreement (benign);Other strong data supporting benign classification
Uncertain significance
(Feb 26, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000552051.4
Submitted: (Jan 07, 2021)
Evidence details
Comment:
This sequence change replaces leucine with proline at codon 454 of the PMS2 protein (p.Leu454Pro). The leucine residue is weakly conserved and there is a … (more)
Uncertain significance
(Jan 07, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV001353133.1
Submitted: (May 19, 2020)
Comment:
This missense variant replaces leucine with proline at codon 454 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure … (more)
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
<i>In Silico</i> Systems Biology Analysis of Variants of Uncertain Significance in Lynch Syndrome Supports the Prioritization of Functional Molecular Validation. Borras E Cancer prevention research (Philadelphia, Pa.) 2017 PMID: 28765196

Text-mined citations for rs772659239...

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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