Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001857359 | SCV002272827 | pathogenic | not provided | 2023-03-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly368 amino acid residue in TULP1. Other variant(s) that disrupt this residue have been observed in individuals with TULP1-related conditions (PMID: 31736247), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TULP1 protein function. ClinVar contains an entry for this variant (Variation ID: 30262). This missense change has been observed in individual(s) with Leber congenital amaurosis and/or retinitis pigmentosa (PMID: 15024725, 25074776; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs387906837, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 368 of the TULP1 protein (p.Gly368Trp). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004586021 | SCV005076366 | pathogenic | Leber congenital amaurosis | 2024-04-11 | criteria provided, single submitter | clinical testing | Variant summary: TULP1 c.1102G>T (p.Gly368Trp) results in a non-conservative amino acid change located in the Tubby, C-terminal domain (IPR000007) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251300 control chromosomes (gnomAD). c.1102G>T has been reported in the literature in multiple individuals affected with Leber Congenital Amaurosis (Hanein_2004, Abbasi_2008, Wang_2013, Jacobson_2014, Karali_2022). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 18432314, 15024725, 25074776, 36460718, 23847139). ClinVar contains an entry for this variant (Variation ID: 30262). Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000023189 | SCV000044480 | pathogenic | Leber congenital amaurosis 15 | 2004-04-01 | no assertion criteria provided | literature only | |
| Laboratory of Genetics in Ophthalmology, |
RCV000023189 | SCV001432535 | pathogenic | Leber congenital amaurosis 15 | no assertion criteria provided | research |