Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000693889 | SCV000822311 | pathogenic | Tuberous sclerosis 2 | 2022-03-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects TSC2 function (PMID: 22903760). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 49929). This missense change has been observed in individual(s) with tuberous sclerosis complex (PMID: 8824881, 10732801, 11112665, 11520734, 22867869, 22903760). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1709 of the TSC2 protein (p.Pro1709Leu). |
| Division of Genomic Medicine, |
RCV000693889 | SCV002559807 | pathogenic | Tuberous sclerosis 2 | 2022-07-19 | criteria provided, single submitter | clinical testing | According to ACMG GL 2015, this variant was detected de novo as a mosaic mutation (PS2), located in the GAP domain (PM1), absent from controls (PM2). Multiple lines of computational evidence support a deleterious effect (PP3), and reported as pathogenic in LOVD database (PP5). |
| Tuberous sclerosis database |
RCV000043196 | SCV000066997 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |