Submissions for variant NM_000314.8(PTEN):c.1026+1G>T

dbSNP: rs786201041

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001220442	SCV001392431	pathogenic	PTEN hamartoma tumor syndrome	2024-11-19	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 8 of the PTEN gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a 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 Cowden or Cowden-like syndrome and overgrowth and intellectual disability (PMID: 21194675, 28475857, 28677221). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 635377). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV000786804	SCV002019541	pathogenic	not provided	2020-03-10	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003453623	SCV004189587	likely pathogenic	Cowden syndrome 1	2023-10-09	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.
MutSpliceDB: a database of splice sites variants effects on splicing, NIH	RCV000786804	SCV000925696	not provided	not provided		no assertion provided	in vitro