Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001057548 | SCV001222046 | pathogenic | not provided | 2023-12-11 | 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 400 of the TULP1 protein (p.Arg400Gln). This variant is present in population databases (rs748972748, gnomAD 0.004%). This missense change has been observed in individuals with retinitis pigmentosa or Leber congenital amaurosis (PMID: 19339744, 23847139; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 852847). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TULP1 protein function. This variant disrupts the p.Arg400 amino acid residue in TULP1. Other variant(s) that disrupt this residue have been observed in individuals with TULP1-related conditions (PMID: 15024725, 24265693, 25074776), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| Ce |
RCV001057548 | SCV001961958 | pathogenic | not provided | 2021-09-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004587030 | SCV005077040 | pathogenic | Leber congenital amaurosis | 2024-04-22 | criteria provided, single submitter | clinical testing | Variant summary: TULP1 c.1199G>A (p.Arg400Gln) results in a conservative amino acid change located in the Tubby, C-terminal domain (IPR000007) of the encoded protein sequence. Four 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 249630 control chromosomes. c.1199G>A has been reported in the literature in multiple individuals affected with Leber Congenital Amaurosis or Retinitis Pigmentosa (e.g. Singh_2009, Wang_2013, Weisschuh_2020). Additionally, this variant segregated with disease in 2 homozygous siblings (Singh_2009). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 29843741, 19339744, 23847139, 32531858). ClinVar contains an entry for this variant (Variation ID: 852847). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Laboratory of Genetics in Ophthalmology, |
RCV001255927 | SCV001432537 | likely pathogenic | Leber congenital amaurosis 15 | no assertion criteria provided | research |