ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.314G>A (p.Cys105Tyr) (rs587782343)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000549505 SCV000930141 likely pathogenic PTEN hamartoma tumor syndrome 2018-11-28 reviewed by expert panel curation PTEN c.314G>A (p.Cys105Tyr) meets criteria to be classified as likely pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). PM2: Absent in large sequenced populations (PMID 27535533). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (internal laboratory contributor ClinVar Organization ID 26957) PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (internal laboratory contributor ClinVar Organization ID 26957)
Ambry Genetics RCV000131280 SCV000186248 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-24 criteria provided, single submitter clinical testing ​The p.C105Y variant (also known as c.314G>A) is located in coding exon 5 of the PTEN gene. This alteration results from a G to A substitution at nucleotide position 314. The cysteine at codon 105 is replaced by tyrosine, an amino acid with highly dissimilar properties. This variant was observed in 1 of 43 individuals who were clinically diagnosed with Bannayan-Riley-Ruvalcaba (BRR) syndrome (Marsh, DJ. Hum Mol Genet. 1999 Aug;8(8):1461-72). In one functional study, the PTEN p.C105Y variant showed no interaction with the LKB1 (STK11) protein in a yeast two-hybrid assay (Mehenni H et al. Hum. Mol. Genet., 2005 Aug;14:2209-19). Based on protein sequence alignment, 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000178758 SCV000230909 uncertain significance not provided 2015-04-16 criteria provided, single submitter clinical testing
Invitae RCV000549505 SCV000645568 uncertain significance PTEN hamartoma tumor syndrome 2017-07-26 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 105 of the PTEN protein (p.Cys105Tyr). 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 Bannayan-Riley-Ruvalcaba syndrome (PMID: 10400993). ClinVar contains an entry for this variant (Variation ID: 142261). An experimental study has reported that this missense change impairs the interaction of PTEN and LKB1 protein in a yeast two-hybrid assay, however the clinical significance of this result is uncertain (PMID: 15987703). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.