Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001189820 | SCV001357186 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-26 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with tryptophan at codon 108 of the PMS2 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on protein structure and function. Splice site prediction tools suggest that this variant may not impact RNA splicing. This variant has been reported in 1 individual affected with colorectal cancer (PMID: 27978560).This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Invitae | RCV002560944 | SCV003240860 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-10-12 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 926913). This missense change has been observed in individual(s) with colon cancer (PMID: 27978560). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 108 of the PMS2 protein (p.Gly108Trp). |