Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004789184 | SCV001427148 | pathogenic | Alport syndrome | 2020-06-11 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0104 - Dominant Negative is a mechanism of disease for this gene. (N) 0108 - This gene is known to be associated with both recessive and dominant disease. Missense variants affecting a glycine within the triple helical repeat are associated with dominant forms of disease, while truncating variants are associated with recessive forms of disease (OMIM, PMID: 30450445). (N) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (exon 29 of 52). (P) 0252 - Variant is homozygous. (N) 0304 - Variant is present in gnomAD v2 <0.01 for a recessive condition (3 heterozygotes, 0 homozygotes). (P) 0701 - Comparable variants have very strong previous evidence for pathogenicity. Other variants also predicted to undergo NMD, have been reported in many homozygous and compound heterozygous patients with recessive Alports syndrome (OMIM, ClinVar, PMID: 29854973). (P) 0803 - Low previous evidence of pathogenicity in unrelated individuals. This variant has been reported in two homozygous families with recessive Alport syndrome (PMID: 31625567). It has also been reported as a VUS (Decipher) and pathogenic (ClinVar) in two heterozygous individuals, where the latter had dominant Alport syndrome. (P) 1205 - Variant is maternally inherited. (N) 1206 - Variant is paternally inherited. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |
| Labcorp Genetics |
RCV001386889 | SCV001587287 | pathogenic | not provided | 2020-08-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in COL4A3 are known to be pathogenic (PMID: 8956999, 24854265). This variant has been observed in individual(s) with clinical features of Alport syndrome (PMID: 30295827, 31625567). ClinVar contains an entry for this variant (Variation ID: 635447). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gly721Valfs*26) in the COL4A3 gene. It is expected to result in an absent or disrupted protein product. |
| Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV000786901 | SCV000925801 | pathogenic | Autosomal dominant Alport syndrome | 2018-11-12 | no assertion criteria provided | clinical testing |