Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001020824 | SCV001182355 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-04 | criteria provided, single submitter | clinical testing | The p.I122S variant (also known as c.365T>G), located in coding exon 5 of the PTEN gene, results from a T to G substitution at nucleotide position 365. The isoleucine at codon 122 is replaced by serine, an amino acid with dissimilar properties. This variant has been detected in a cohort of patients who met clinical diagnostic criteria for Cowden syndrome (CS) or relaxed clinical diagnostic criteria for CS-like (Nizialek EA et al. Eur. J. Hum. Genet., 2015 Nov;23:1538-43). 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. |
| Invitae | RCV001214316 | SCV001385991 | uncertain significance | PTEN hamartoma tumor syndrome | 2022-07-25 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 122 of the PTEN protein (p.Ile122Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Cowden or Cowden-like syndrome (PMID: 25669429). ClinVar contains an entry for this variant (Variation ID: 824039). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). Experimental studies have shown that this missense change affects PTEN function (PMID: 21828076). 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. |
| Myriad Genetics, |
RCV003455115 | SCV004188749 | likely pathogenic | Cowden syndrome 1 | 2023-09-27 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 25669429, Myriad internal data]. This variant is expected to disrupt protein structure [Myriad internal data]. Functional studies indicate this variant impacts protein function [29785012]. |