Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001386008 | SCV001586081 | pathogenic | not provided | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 482 of the TULP1 protein (p.Arg482Gln). This variant is present in population databases (rs146311742, gnomAD 0.0009%). This missense change has been observed in individuals with autosomal recessive retinitis pigmentosa (PMID: 22665969, 30950243). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 977980). 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. For these reasons, this variant has been classified as Pathogenic. |
| 3billion | RCV001810007 | SCV002058886 | pathogenic | Retinitis pigmentosa 14 | 2022-01-03 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported to be associated with TULP1 related disorder (ClinVar ID: VCV000977980, PMID:22665969, PS1_P). The variant has been reported to be in trans as homozygous in at least one similarly affected unrelated individual (PMID: 22665969,PM3_P). It was co-segregated with Retinitis pigmentosa 14 in multiple affected family members with additional meioses meeting strong evidence levels (PMID: 22665969, 30950243) (PP1_S). A different missense change at the same codon has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000007363, PMID:17620573, PM5_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.942, PP3_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000004, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Laboratory of Genetics in Ophthalmology, |
RCV001255931 | SCV001432542 | likely pathogenic | Leber congenital amaurosis 15 | no assertion criteria provided | research |