Submissions for variant NM_000314.8(PTEN):c.801+1G>A

dbSNP: rs786204873

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000169813	SCV000222130	pathogenic	not provided	2023-06-21	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); This variant is associated with the following publications: (PMID: 11071384)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001384751	SCV001584395	pathogenic	PTEN hamartoma tumor syndrome	2024-05-23	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 7 of the PTEN gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with PTEN hamartoma tumor syndrome (PMID: 9600246, 10234502, 11071384, 11238682). ClinVar contains an entry for this variant (Variation ID: 189420). Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 11071384). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV003454433	SCV004188769	likely pathogenic	Cowden syndrome 1	2023-09-29	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.