Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000672563 | SCV000797677 | likely pathogenic | Autosomal recessive Alport syndrome | 2018-02-06 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002499182 | SCV002809918 | pathogenic | Autosomal dominant Alport syndrome; Autosomal recessive Alport syndrome; Benign familial hematuria | 2022-05-25 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003558517 | SCV004294019 | pathogenic | not provided | 2023-06-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the COL4A3 protein in which other variant(s) (p.Gly777Asp) have been determined to be pathogenic (PMID: 26633401, 27904025). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 556542). This variant has been observed in individual(s) with Alport syndrome (PMID: 24052634, 24854265, 28780565). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This variant, c.2323_2340del, results in the deletion of 6 amino acid(s) of the COL4A3 protein (p.Leu775_Gly780del), but otherwise preserves the integrity of the reading frame. |
| Sydney Genome Diagnostics, |
RCV001328058 | SCV001449245 | likely pathogenic | Hematuria | 2018-08-28 | no assertion criteria provided | clinical testing | This patient is heterozygous for the c.2323_2340del (p.Leu775_Gly780del) variant in exon 30 of the COL4A3 gene. This variant results in an inframe deletion of six amino acid residues (Leu-Pro-Gly-Leu-Pro-Gly) in the triple helical domain of the alpha 3 chain of type IV collagen. To our knowledge, this nucleotide variant has not been previously reported. However, a variant involving an inframe deletion of the same six amino acids, c.2313_2330del (p.Leu775_Gly780del), has been previously reported in trans with another pathogenic COL4A3 variant in a patient with autosomal recessive Alport syndrome in the literature (Storey et al 2013 J Am Soc Nephrol 24:1945-1954). This variant is likely to be pathogenic as an inframe deletion of six amino acids is likely to disrupt the folding of the triple helix domain. |