Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV001073666 | SCV001239218 | pathogenic | Retinal dystrophy | 2019-08-09 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001223788 | SCV001395952 | pathogenic | Leber congenital amaurosis 13 | 2023-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 126 of the RDH12 protein (p.Ala126Val). This variant is present in population databases (rs202126574, gnomAD 0.006%). This missense change has been observed in individuals with autosomal recessive RDH12-related disease (PMID: 19140180, 30134391). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2061). 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 RDH12 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV001558134 | SCV001780019 | likely pathogenic | not provided | 2022-12-28 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19140180, 24752437, 26667666, 26261414, 31980526, 31054281, 31456290, 33090715, 33629268, 35006499, 31630094, 33691693, 30134391) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155010 | SCV003844332 | pathogenic | Leber congenital amaurosis | 2023-02-28 | criteria provided, single submitter | clinical testing | Variant summary: RDH12 c.377C>T (p.Ala126Val) results in a non-conservative amino acid change in 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 1.2e-05 in 251476 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.377C>T has been reported in the literature in multiple individuals affected with Leber Congenital Amaurosis (e.g., Kuniyoshi_2014, Sharon_2015, Benayoun_2009, Aleman_2018), and the variant was found to segregate with disease in multiple unrelated families. These data indicate that the variant is very likely to be associated with disease. Four ClinVar submitters (evaluation after 2014) have cited the variant, and all laboratories classified the variant as pathogenic (n = 3) or likely pathogenic (n = 1). Based on the evidence outlined above, the variant was classified as pathogenic. |
Baylor Genetics | RCV001223788 | SCV004208562 | pathogenic | Leber congenital amaurosis 13 | 2023-10-19 | criteria provided, single submitter | clinical testing | |
Dept Of Ophthalmology, |
RCV001073666 | SCV004707751 | uncertain significance | Retinal dystrophy | 2023-10-01 | criteria provided, single submitter | research | |
OMIM | RCV000002142 | SCV000022300 | pathogenic | Retinitis pigmentosa 53 | 2009-02-15 | no assertion criteria provided | literature only | |
Department of Ophthalmology and Visual Sciences Kyoto University | RCV000132691 | SCV000172644 | pathogenic | Retinitis pigmentosa | no assertion criteria provided | not provided | Converted during submission to Pathogenic. | |
Sharon lab, |
RCV000132691 | SCV001161224 | pathogenic | Retinitis pigmentosa | 2019-06-23 | no assertion criteria provided | research |