ClinVar Miner

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

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
3billion RCV001808854 SCV002059028 likely pathogenic Macrocephaly-autism syndrome 2022-01-03 criteria provided, single submitter clinical testing Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region (PVS1_VS).It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Ambry Genetics RCV002334703 SCV002642113 pathogenic Hereditary cancer-predisposing syndrome 2022-07-26 criteria provided, single submitter clinical testing The c.493-1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide upstream from coding exon 6 of the PTEN gene. Another alteration impacting the same acceptor site (c.493-2A>G) has been shown to have a similar impact on splicing and has been reported in multiple individuals with personal and/or family history consistent with PTEN hamartoma tumor syndrome, including Cowden syndrome (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). 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.
Myriad Genetics, Inc. RCV003451954 SCV004188795 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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