Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001305530 | SCV001494868 | uncertain significance | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 579 of the IMPG1 protein (p.Leu579Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant IMPG1-related conditions (PMID: 32817297). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1008228). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. |
SIB Swiss Institute of Bioinformatics | RCV001644981 | SCV002499758 | likely pathogenic | Benign concentric annular macular dystrophy | 2022-03-18 | criteria provided, single submitter | curation | This variant is interpreted as likely pathogenic for Retinitis pigmentosa 91, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1 upgraded to strong); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3). |
3billion | RCV001644981 | SCV005903796 | likely pathogenic | Benign concentric annular macular dystrophy | 2024-02-19 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Missense variant In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.78 (>=0.6, sensitivity 0.68 and specificity 0.92); 3Cnet: 0.84 (>=0.6, sensitivity 0.72 and precision 0.9)]. Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV001008228 /PMID: 23993198). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |
OMIM | RCV001644981 | SCV001852750 | pathogenic | Benign concentric annular macular dystrophy | 2021-09-10 | no assertion criteria provided | literature only |