Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000724695 | SCV000232537 | uncertain significance | not provided | 2015-03-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000724695 | SCV000243491 | likely pathogenic | not provided | 2022-05-18 | criteria provided, single submitter | clinical testing | Exon-1 splice site variant in a gene for which loss of function is a known mechanism of disease, and splice predictors support a deleterious effect; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 9536098, 21309039, 29196670, 33679864, 17576681, 18830229) |
| Invitae | RCV000821093 | SCV000961836 | pathogenic | Tuberous sclerosis 1 | 2021-08-28 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with tuberous sclerosis (PMID: 18830229, 29196670; Invitae). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. 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. Experimental studies have shown that this missense change does not substantially affect TSC1 function (PMID: 18830229, 21309039). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 49094). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with lysine at codon 246 of the TSC1 protein (p.Arg246Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. This variant also falls at the last nucleotide of exon 8, which is part of the consensus splice site for this exon. |
| Genome- |
RCV000821093 | SCV002040152 | likely pathogenic | Tuberous sclerosis 1 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Tuberous sclerosis database |
RCV000042348 | SCV000066137 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |