Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000630078 | SCV000751034 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-01-14 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PMS2-related disease. This variant is present in population databases (rs372172981, ExAC 0.01%). This sequence change replaces tyrosine with cysteine at codon 310 of the PMS2 protein (p.Tyr310Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. |
Ambry Genetics | RCV001019128 | SCV001180450 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-15 | criteria provided, single submitter | clinical testing | The p.Y310C variant (also known as c.929A>G), located in coding exon 9 of the PMS2 gene, results from an A to G substitution at nucleotide position 929. The tyrosine at codon 310 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002507058 | SCV002816859 | uncertain significance | Lynch syndrome 4; Mismatch repair cancer syndrome 4 | 2021-09-23 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004002790 | SCV004838199 | uncertain significance | Lynch syndrome | 2023-11-20 | criteria provided, single submitter | clinical testing | This missense variant replaces tyrosine with cysteine at codon 310 of the PMS2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 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. |