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NM_000535.7(PMS2):c.1187T>C (p.Met396Thr) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 11, 2014
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:
RCV000165645.1

Allele description

NM_000535.7(PMS2):c.1187T>C (p.Met396Thr)

Gene:
PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p22.1
Genomic location:
Preferred name:
NM_000535.7(PMS2):c.1187T>C (p.Met396Thr)
HGVS:
  • NC_000007.14:g.5987578A>G
  • NG_008466.1:g.26529T>C
  • NM_000535.7:c.1187T>CMANE SELECT
  • NM_001322003.2:c.782T>C
  • NM_001322004.2:c.782T>C
  • NM_001322005.2:c.782T>C
  • NM_001322006.2:c.1031T>C
  • NM_001322007.2:c.869T>C
  • NM_001322008.2:c.869T>C
  • NM_001322009.2:c.782T>C
  • NM_001322010.2:c.626T>C
  • NM_001322011.2:c.254T>C
  • NM_001322012.2:c.254T>C
  • NM_001322013.2:c.614T>C
  • NM_001322014.2:c.1187T>C
  • NM_001322015.2:c.878T>C
  • NP_000526.2:p.Met396Thr
  • NP_001308932.1:p.Met261Thr
  • NP_001308933.1:p.Met261Thr
  • NP_001308934.1:p.Met261Thr
  • NP_001308935.1:p.Met344Thr
  • NP_001308936.1:p.Met290Thr
  • NP_001308937.1:p.Met290Thr
  • NP_001308938.1:p.Met261Thr
  • NP_001308939.1:p.Met209Thr
  • NP_001308940.1:p.Met85Thr
  • NP_001308941.1:p.Met85Thr
  • NP_001308942.1:p.Met205Thr
  • NP_001308943.1:p.Met396Thr
  • NP_001308944.1:p.Met293Thr
  • LRG_161t1:c.1187T>C
  • LRG_161:g.26529T>C
  • NC_000007.13:g.6027209A>G
  • NM_000535.5:c.1187T>C
  • NR_136154.1:n.1274T>C
  • p.M396T
Protein change:
M205T
Links:
dbSNP: rs786202704
NCBI 1000 Genomes Browser:
rs786202704
Molecular consequence:
  • NM_000535.7:c.1187T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322003.2:c.782T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322004.2:c.782T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322005.2:c.782T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322006.2:c.1031T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322007.2:c.869T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322008.2:c.869T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322009.2:c.782T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322010.2:c.626T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322011.2:c.254T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322012.2:c.254T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322013.2:c.614T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322014.2:c.1187T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322015.2:c.878T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_136154.1:n.1274T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000216381Ambry Genetics
criteria provided, single submitter

(Ambry Autosomal Dominant and X-Linked criteria (10/2015))
Uncertain significance
(Aug 11, 2014)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Details of each submission

From Ambry Genetics, SCV000216381.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The p.M396T variant (also known as c.1187T>C), located in coding exon 11 of the PMS2 gene, results from a T to C substitution at nucleotide position 1187. The methionine at codon 396 is replaced by threonine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6424 samples (12848 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.004% (greater than 23,000 alleles tested) in our clinical cohort. Based on protein sequence alignment, this amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.M396T remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Nov 5, 2022