Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000221346 | SCV000273059 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-17 | criteria provided, single submitter | clinical testing | The p.P150L variant (also known as c.449C>T), located in coding exon 5 of the PMS2 gene, results from a C to T substitution at nucleotide position 449. The proline at codon 150 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV000685605 | SCV000813090 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-08-17 | 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: 229736). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is present in population databases (rs778119115, gnomAD 0.0009%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 150 of the PMS2 protein (p.Pro150Leu). |
Color Diagnostics, |
RCV000221346 | SCV001734750 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-06 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 150 of the PMS2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has been identified in 1/250968 chromosomes 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. |
Sema4, |
RCV000221346 | SCV002530345 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-12 | criteria provided, single submitter | curation | |
Institute for Biomarker Research, |
RCV000221346 | SCV004227998 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-31 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003997764 | SCV004839973 | uncertain significance | Lynch syndrome | 2023-10-02 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 150 of the PMS2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has been identified in 1/250968 chromosomes 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. |