Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000220547 | SCV000278051 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2016-08-17 | criteria provided, single submitter | clinical testing | Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Well-characterized mutation at same position;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Other data supporting pathogenic classification |
| Invitae | RCV000471590 | SCV000541631 | likely pathogenic | PTEN hamartoma tumor syndrome | 2016-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with tyrosine at codon 124 of the PTEN protein (p.Cys124Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Cowden syndrome (PMID: 15211648). ClinVar contains an entry for this variant (Variation ID: 233631). Cysteine 124 is a catalytically critical residue located in the active site phosphate binding loop of the PTEN protein (PMID: 10555148, 17324556). While experimental studies have not been reported for this particular variant, different missense substitutions at this codon (p.Cys124Ala, p.Cys124Ser, p.Cys124Asn, p.Cys124Arg) have been reported in individuals affected with Cowden syndrome, and shown to abolish PTEN phosphatase activity (PMID: 20685300, 21828076, 25647146, 17324556, 12938083, 21194675). In summary, this variant has been reported in an affected individual and is expected to disrupt protein function. However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic. |