ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1360C>T (p.Leu454=)

gnomAD frequency: 0.00001  dbSNP: rs1338448094
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001011177 SCV001171468 likely benign Hereditary cancer-predisposing syndrome 2018-01-23 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV002060092 SCV002383213 likely benign Hereditary nonpolyposis colorectal neoplasms 2022-10-17 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003320665 SCV004025118 likely benign not specified 2023-08-15 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000501859 SCV000592932 likely benign Endometrial carcinoma no assertion criteria provided clinical testing PMS2, EXON11, c.1360C>T, p.Leu454Leu, Predicted Benign (ACMG 4) The PMS2 c.1360C>T variant was not identified in the literature nor was it identified in the COGR, HMGD, Mut, MMR, INSiGHT Colon Cancer or Zheilang Coln Cancer databases. It is not listed in the dbSNP database and no frequency information was provided, thus the prevalence of this variant in the general population could not be determined. The p.Leu454 residue is not conserved in mammals and the variant amino acid Leu is present in mouse and chicken, increasing the likelihood that this variant does not have clinical significance. Computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein. The p.Leu454Leu variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as predicted benign.

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