Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002034774 | SCV002218444 | uncertain significance | not provided | 2024-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1224 of the COL4A1 protein (p.Pro1224Leu). This variant is present in population databases (rs775810147, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with COL4A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1344677). 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 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004526150 | SCV005040541 | uncertain significance | not specified | 2024-03-01 | criteria provided, single submitter | clinical testing | Variant summary: COL4A1 c.3671C>T (p.Pro1224Leu) results in a non-conservative amino acid change in 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 6.1e-05 in 243918 control chromosomes. This frequency does not allow conclusion about variant significance. To our knowledge, no occurrence of c.3671C>T in individuals affected with Porencephaly 1 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1344677). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Fulgent Genetics, |
RCV005006091 | SCV005632877 | 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 | 2024-05-28 | criteria provided, single submitter | clinical testing | |
| Yale Center for Mendelian Genomics, |
RCV001849678 | SCV002106640 | likely pathogenic | Congenital anomaly of kidney and urinary tract | 2019-06-22 | no assertion criteria provided | literature only |