Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000437521 | SCV000517312 | pathogenic | not provided | 2021-11-22 | criteria provided, single submitter | clinical testing | Affects a glycine residue in a Gly-X-Y motif in the triple-helical region of the COL4A1 gene, where the majority of pathogenic missense variants occur and is predicted to disrupt normal protein folding and function (HGMD); Not observed in large population cohorts (gnomAD); 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: 25457163, 28098148, 24628545, 30837194, 31051113, 33527515, 31848469, 16107487, 17938367, 23394911) |
Ambry Genetics | RCV000623415 | SCV000741072 | pathogenic | Inborn genetic diseases | 2023-08-10 | criteria provided, single submitter | clinical testing | The c.2317G>A (p.G773R) alteration is located in coding exon 30 of the COL4A1 gene. This alteration results from a G to A substitution at nucleotide position 2317, causing the glycine (G) at amino acid position 773 to be replaced by an arginine (R). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been determined to be the result of a de novo mutation and has been reported as heterozygous in multiple individuals with features consistent with COL4A1-related disorder (Deml, 2014; Colin, 2014; Slavotinek, 2015; Hausman-Kedem, 2021). Another alteration that causes the same amino acid change c.2317G>C (p.G773R) has also been detected in two related individuals with clinical features consistent with COL4A1-related disorder (Shah, 2012). This amino acid position is highly conserved in available vertebrate species. The p.G773 amino acid is located within the triple-helical domain of the collagen IV alpha 1 chain, and this alteration affects one of the highly conserved glycine residues in the Gly-X-Y motif that make up this domain (Ramshaw, 1998). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. |
Institute of Medical Genetics and Applied Genomics, |
RCV000437521 | SCV001447290 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
3billion | RCV002283479 | SCV002572869 | pathogenic | Brain small vessel disease 1 with or without ocular anomalies | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.97; 3Cnet: 0.87). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000379845). The variant has been previously reported as de novo in at least two similarly affected unrelated individuals (PMID: 25457163 , 33527515). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 22574627 , 24374867 , 24628545 , 25457163 , 31051113 , 33353976 , 33527515). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |
Fulgent Genetics, |
RCV002502498 | SCV002804545 | pathogenic | Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome; Brain small vessel disease 1 with or without ocular anomalies; Hemorrhage, intracerebral, susceptibility to; Retinal arterial tortuosity; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant | 2021-07-14 | criteria provided, single submitter | clinical testing | |
Molecular Medicine, |
RCV002283479 | SCV004022318 | likely pathogenic | Brain small vessel disease 1 with or without ocular anomalies | 2023-07-28 | criteria provided, single submitter | research |