Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Herman Laboratory, |
RCV000490594 | SCV000579265 | pathogenic | PTEN hamartoma tumor syndrome | 2017-03-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000491885 | SCV000580009 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-08-22 | criteria provided, single submitter | clinical testing | The c.253+1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide after coding exon 4 of the PTEN gene. This mutation has been reported in multiple individuals with Cowden syndrome and has also been observed to segregate with disease in multiple families (Nelen MR et al. Hum. Mol. Genet. 1997 Aug; 6(8):1383-7; Tan MH et al. Am. J. Hum. Genet. 2011 Jan; 88(1):42-56; Busch RM et al. Genet. Med. 2013 Jul; 15(7):548-53; Nizialek EA et al. Eur. J. Hum. Genet. 2015 Nov;23:1538-43). In addition to the clinical data presented in the literature, 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, |
RCV003316641 | SCV004018642 | pathogenic | Cowden syndrome 1 | 2023-05-12 | criteria provided, single submitter | clinical testing | This variant is considered 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. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 34386506, 28677221, 23470840, 29931205, 33723755]. mRNA analysis has demonstrated abnormal mRNA splicing occurs [PMID: 28677221]. |