Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003511465 | SCV004295292 | likely pathogenic | PTEN hamartoma tumor syndrome | 2024-08-05 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 27 of the PTEN protein (p.Tyr27Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of PTEN hamartoma tumor syndrome (PMID: 29625052, 29706633, 36451132; Invitae). 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. Experimental studies have shown that this missense change affects PTEN function (PMID: 29706633). This variant disrupts the p.Tyr27 amino acid residue in PTEN. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Ambry Genetics | RCV004943096 | SCV005482017 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-08-22 | criteria provided, single submitter | clinical testing | The c.79T>A variant (also known as p.Y27N), located in coding exon 1 of the PTEN gene, results from a T to A substitution at nucleotide position 79. The amino acid change results in tyrosine to asparagine at codon 27, an amino acid with dissimilar properties. This variant was reported in multiple individuals with features consistent with PTEN hamartoma tumor syndrome (Ngeow J et al. J Clin Oncol, 2014 Jun;32:1818-24; Huang KL et al. Cell, 2018 Apr;173:355-370.e14; Caroleo AM et al. Front Mol Neurosci, 2023 Aug;16:1228389). In a massively parallel functional assay using a humanized yeast model, lipid phosphatase activity for this variant was functionally deficient (Mighell TL et al. Am. J. Hum. Genet. 2018 05;102:943-955). This missense alteration is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI: dx.doi.org/10/1016/j.ajhg.2009.03.010)). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |