Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001061939 | SCV001226704 | pathogenic | not provided | 2023-11-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Phe1446Cysfs*63) in the COL4A3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL4A3 are known to be pathogenic (PMID: 8956999, 24854265, 26809805, 27281700). This variant is present in population databases (rs776244020, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with COL4A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 856468). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001532939 | SCV001748751 | likely pathogenic | Autosomal recessive Alport syndrome | 2021-06-28 | criteria provided, single submitter | clinical testing | Variant summary: COL4A3 c.4337_4338delTT (p.Phe1446CysfsX63) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 249536 control chromosomes. To our knowledge, no occurrence of c.4337_4338delTT in individuals affected with Alport Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Gene |
RCV001061939 | SCV003918644 | uncertain significance | not provided | 2022-10-13 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge |