Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002323108 | SCV002632630 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-07-20 | criteria provided, single submitter | clinical testing | The p.C136F pathogenic mutation (also known as c.407G>T), located in coding exon 5 of the PTEN gene, results from a G to T substitution at nucleotide position 407. The cysteine at codon 136 is replaced by phenylalanine, an amino acid with highly dissimilar properties. In a functional study, this variant demonstrated deficient phosphatase activity (Mighell TL et al. Am. J. Hum. Genet., 2018 05;102:943-955). Two other alterations at the same codon, p.C136R (c.406T>C) and p.C136Y (c.407G>A), have been detected in individuals with features consistent with PTEN Hamartoma Tumor Syndrome (PHTS) (Kubo Y et al. Br. J. Dermatol. 2000 Jun;142(6):1100-5; Galatola M et al. BMC Med. Genet., 2012 Apr;13:28; Matsumoto K et al. Diagn. Pathol. 2015 Sep;10:172; Ambry internal data). 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 variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |