Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000645055 | SCV000766795 | likely pathogenic | PTEN hamartoma tumor syndrome | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 267 of the PTEN protein (p.Lys267Asn). This variant also falls at the last nucleotide of exon 7, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with PTEN hamartoma tumor syndrome (PMID: 30528446). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 536549). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Ce |
RCV001312161 | SCV001502627 | likely pathogenic | not provided | 2020-12-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001312161 | SCV001805396 | likely pathogenic | not provided | 2019-05-08 | criteria provided, single submitter | clinical testing | In silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect; In addition, in silico predictors and evolutionary conservation suggest the missense change may have a deleterious effect on the protein. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown; Splice variants affecting the same splice donor site reported in the Human Gene Mutation Database in individuals with PTEN hamartoma tumor syndrome (PHTS) (Stenson et al., 2014); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 30528446) |
| Ambry Genetics | RCV002422336 | SCV002679832 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-24 | criteria provided, single submitter | clinical testing | The c.801G>T pathogenic mutation (also known as p.K267N), located in coding exon 7 of the PTEN gene, results from a G to T substitution at nucleotide position 801. The amino acid change results in lysine to asparagine at codon 267, an amino acid with similar properties. However, this change occurs in the last base pair of coding exon 7, which makes it likely to have some effect on normal mRNA splicing. This alteration has been reported as de novo in a two-year-old male diagnosed with macrocephaly, vascular malformations, enlarged perivascular spaces and developmental delay (Ciaccio C et al. Eur J Med Genet, 2019 Dec;62:103596). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001312161 | SCV002774714 | uncertain significance | not provided | 2021-09-01 | criteria provided, single submitter | clinical testing |