Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000657672 | SCV000779421 | pathogenic | not provided | 2016-03-02 | criteria provided, single submitter | clinical testing | This variant is denoted PMS2 c.986C>G at the cDNA level and p.Ser329Ter (S329X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TGA) , and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic. |
Invitae | RCV001381062 | SCV001579314 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-03-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 545975). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser329*) 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). |
Ambry Genetics | RCV002386127 | SCV002689345 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-08-30 | criteria provided, single submitter | clinical testing | The p.S329* pathogenic mutation (also known as c.986C>G), located in coding exon 9 of the PMS2 gene, results from a C to G substitution at nucleotide position 986. This changes the amino acid from a serine to a stop codon within coding exon 9. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Myriad Genetics, |
RCV003316781 | SCV004018946 | pathogenic | Lynch syndrome 4 | 2023-03-28 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
ARUP Laboratories, |
RCV000657672 | SCV004564458 | pathogenic | not provided | 2023-04-26 | criteria provided, single submitter | clinical testing | The PMS2 c.986C>G; p.Ser329Ter variant (rs1461669945), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 545975). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. |