ClinVar Miner

Submissions for variant NM_003322.6(TULP1):c.1063G>A (p.Asp355Asn)

gnomAD frequency: 0.00002  dbSNP: rs1085307806
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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, Institut des Neurosciences de Montpellier 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.