Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000485204 | SCV000572519 | likely pathogenic | not provided | 2016-12-30 | criteria provided, single submitter | clinical testing | The c.3068_3069delCA variant in the COL4A3 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.3068_3069delCA variant causes a frameshift starting with codon Proline 1023, changes this amino acid to a Arginine residue, and creates a premature Stop codon at position 3 of the new reading frame, denoted p.Pro1023ArgfsX3. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. As an alternate mechanism, this variant is predicted to destroy the natural splice donor site in intron 36, which may cause abnormal splicing. However, in the absence of RNA/functional studies, the actual effect of c.3068_3069delCA is unknown. The c.3068_3069delCA variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.3068_3069delCA as a likely pathogenic variant. |
| Labcorp Genetics |
RCV000485204 | SCV002231976 | pathogenic | not provided | 2021-10-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Pro1023Argfs*3) 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 not present in population databases (ExAC no frequency). 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: 422920). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. |
| Fulgent Genetics, |
RCV002506176 | SCV002810923 | likely pathogenic | Autosomal dominant Alport syndrome; Autosomal recessive Alport syndrome; Benign familial hematuria | 2022-02-01 | criteria provided, single submitter | clinical testing |