Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000657310 | SCV000779041 | pathogenic | not provided | 2017-04-06 | criteria provided, single submitter | clinical testing | This deletion of one nucleotide in PMS2 is denoted c.1532delC at the cDNA level and p.Thr511ArgfsX84 (T511RfsX84) at the protein level. The normal sequence, with the base that is deleted in brackets, is GACA[delC]GGGC. The deletion causes a frameshift which changes a Threonine to an Arginine at codon 511, and creates a premature stop codon at position 84 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic. |
Invitae | RCV000695167 | SCV000823649 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-10-27 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with PMS2-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 545777). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr511Argfs*84) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). |