Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002368934 | SCV002657289 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-01-12 | criteria provided, single submitter | clinical testing | The c.634_634+1delAG pathogenic mutation results from a deletion of two nucleotides between positions 634 and 634+1 and involves the canonical splice donor site after coding exon 6 of the PTEN gene. Other alterations impacting the same donor site (c.634+1G>T and c.634+1G>C) have been detected in individuals meeting Cowden syndrome or CS-like clinical criteria (Agrawal et al. Hum Mol Genet 2005 Aug;14(16):2459-68; Chen HJ et al. Hum Mutat 2017 10;38(10):1372-7; Busch RM et al. Genet Med 2013 Jul;15(7):548-53; Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). 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 interpreted as a disease-causing mutation. |