Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000421365 | SCV000536240 | uncertain significance | not provided | 2017-01-19 | criteria provided, single submitter | clinical testing | The P887S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P887S variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P887S variant is a non-conservative amino acid substitution that occurs at a position predicted to be in the triple helical region that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (G882D, G888R, G891D) have been reported in the literature and/or identified at GeneDx in association with neurodevelopmental disorders, supporting the functional importance of this region of the protein. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV000421365 | SCV002297024 | uncertain significance | not provided | 2023-05-29 | criteria provided, single submitter | clinical testing | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 392901). This variant has not been reported in the literature in individuals affected with COL4A1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 887 of the COL4A1 protein (p.Pro887Ser). |
| Fulgent Genetics, |
RCV002481347 | SCV002775892 | uncertain significance | 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 | 2022-03-04 | criteria provided, single submitter | clinical testing |