Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002238606 | SCV002511664 | uncertain significance | not specified | 2024-05-16 | criteria provided, single submitter | clinical testing | Variant summary: TULP1 c.1246C>T (p.Arg416Cys) 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 7.5e-06 in 1599866 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in TULP1 causing Leber Congenital Amaurosis (7.5e-06 vs 0.0005), allowing no conclusion about variant significance. c.1246C>T has been reported in the literature in the compound heterozygous state in individuals affected with retinitis pigmentosa (example, Katagiri_2014, Koyanagi_2019, Suga_2022). These data indicate that the variant may 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: 25268133, 31213501, 36284460). ClinVar contains an entry for this variant (Variation ID: 1683297). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Labcorp Genetics |
RCV003560879 | SCV004293298 | pathogenic | not provided | 2023-06-20 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 25268133, 31213501). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. 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: 1683297). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 416 of the TULP1 protein (p.Arg416Cys). |
| Dept Of Ophthalmology, |
RCV003889106 | SCV004707282 | likely pathogenic | Retinal dystrophy | 2023-10-01 | criteria provided, single submitter | research |