Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000085874 | SCV000321334 | likely pathogenic | not provided | 2018-10-18 | criteria provided, single submitter | clinical testing | The P309R variant in the ABCA4 gene has been reported previously in association with autosomal recessive Stargardt disease when present with another disease-causing variant in the ABCA4 gene (Briggs et al., 2001; Cideciyan et al., 2009; Zernant et al., 2014; Carss et al., 2017). The P309R variant is observed in 39/24,022 (0.1624%) alleles from individuals of African background in large population cohorts and no individuals were reported to be homozygous (Lek et al., 2016). The P309R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret P309R as a likely pathogenic variant. |
Blueprint Genetics | RCV001075838 | SCV001241477 | likely pathogenic | Retinal dystrophy | 2019-08-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000085874 | SCV001382437 | uncertain significance | not provided | 2019-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with arginine at codon 309 of the ABCA4 protein (p.Pro309Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is present in population databases (rs61748545, ExAC 0.2%). This variant has been observed in individuals with Stargardt disease (PMID: 25066811, 22247458) and in an individual with macular dystrophy (PMID: 28041643). ClinVar contains an entry for this variant (Variation ID: 99513). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). 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. |
Retina International | RCV000085874 | SCV000118017 | not provided | not provided | no assertion provided | not provided | ||
NIHR Bioresource Rare Diseases, |
RCV000504769 | SCV000599027 | likely pathogenic | Macular dystrophy | 2015-01-01 | no assertion criteria provided | research |