Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000489746 | SCV000577339 | likely pathogenic | not provided | 2017-04-04 | criteria provided, single submitter | clinical testing | The D355N variant in the TULP1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D355N variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D355N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in the same residue (D355V) has been reported in the compound heterozygous state in a patient with Leber congenital amaurosis (Wang et al., 2013), supporting the functional importance of this region of the protein. We interpret D355N as a likely pathogenic variant. |
INSERM U1051, |
RCV001249894 | SCV001424169 | likely pathogenic | Retinitis pigmentosa | 2020-06-24 | criteria provided, single submitter | research | |
Invitae | RCV000489746 | SCV002118219 | uncertain significance | not provided | 2022-03-23 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 355 of the TULP1 protein (p.Asp355Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 33576794). ClinVar contains an entry for this variant (Variation ID: 426801). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). This variant disrupts the p.Asp355 amino acid residue in TULP1. Other variant(s) that disrupt this residue have been observed in individuals with TULP1-related conditions (PMID: 23847139), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |