ClinVar Miner

Submissions for variant NM_000314.8(PTEN):c.493-1G>C

dbSNP: rs786204862
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001023286 SCV001185139 pathogenic Hereditary cancer-predisposing syndrome 2018-06-18 criteria provided, single submitter clinical testing The c.493-1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide upstream from coding exon 6 of the PTEN gene. This alteration has been identified in an individual with features of Cowden syndrome (Ambry internal data). Another alteration at the same splice acceptor site, c.493-2A>G, has been reported as pathogenic based on identification in an individual satisfying operational diagnostic criteria for Cowden syndrome (Ambry internal data). In addition to the clinical data presented, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
GeneDx RCV003332284 SCV004039933 pathogenic not provided 2023-04-01 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Identified in individuals with PTEN-related cancers or clinical features of PTEN Hamartoma Tumor syndrome in published literature and previously tested at GeneDx (Momozawa et al., 2018; Fujita et al., 2020; Pena-Couso et al., 2022); This variant is associated with the following publications: (PMID: 33309985, 35227301, 30287823)
Myriad Genetics, Inc. RCV003455123 SCV004188789 likely pathogenic Cowden syndrome 1 2023-09-28 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.

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