Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001766260 | SCV002008102 | uncertain significance | not provided | 2023-05-01 | criteria provided, single submitter | clinical testing | Identified in patients with small vessel disease and ischemic stroke in the published literature (Tan et al., 2019; Hrtl et al., 2022); 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: 36411388, 31719132) |
| Labcorp Genetics |
RCV001766260 | SCV002195634 | uncertain significance | not provided | 2025-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1657 of the COL4A1 protein (p.Thr1657Met). This variant is present in population databases (rs779139113, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of COL4A1-related conditions (PMID: 31719132, 36411388). ClinVar contains an entry for this variant (Variation ID: 1316354). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COL4A1 protein function. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323929 | SCV004029342 | uncertain significance | not specified | 2023-07-14 | criteria provided, single submitter | clinical testing | Variant summary: COL4A1 c.4970C>T (p.Thr1657Met) results in a non-conservative amino acid change located in the Collagen IV, non-collagenous (IPR001442) of 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 3.2e-05 in 250574 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4970C>T has been reported in the literature in individuals affected with Small Vessel disease and Stroke (Hartberger_2022, Tan_2019). These reports do not provide unequivocal conclusions about association of the variant with Porencephaly 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31719132, 36411388). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Fulgent Genetics, |
RCV005005280 | SCV005632818 | 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 | 2024-01-03 | criteria provided, single submitter | clinical testing |