Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | 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). |
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 |