Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Medical Genetics, |
RCV000789032 | SCV000928369 | pathogenic | X-linked Alport syndrome | 2018-05-24 | criteria provided, single submitter | clinical testing | PVS1,PM1,PM2,PP2 |
Kasturba Medical College, |
RCV000789032 | SCV003803639 | pathogenic | X-linked Alport syndrome | criteria provided, single submitter | clinical testing | ||
King Laboratory, |
RCV000789032 | SCV003844195 | pathogenic | X-linked Alport syndrome | 2023-02-28 | criteria provided, single submitter | research | This variant was found in hemizygosity in a male patient with Alport syndrome, in a study of pediatric hearing loss conducted by the King Laboratory (Carlson RJ et al. JAMA-OtoHNS 2023). This patient has a maternal uncle with Alport syndrome, and his mother and grandmother also have renal abnormalities. The patient’s family has no other history of hearing loss. This variant is a single base pair deletion that causes a frameshift leading to the addition of 93 incorrect amino acids and an early stop at position 1547 of the 1691 amino acid COL4A5 protein. As of January 2023, this variant has been reported to ClinVar as pathogenic and is not found on gnomAD. Based on the prediction that this variant leads to a truncated protein, x-linked recessive inheritance pattern in the family, and goodness of fit of genotype to phenotype, we conclude that this variant is pathogenic. |
Invitae | RCV003660835 | SCV004376170 | pathogenic | not provided | 2023-03-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 637042). This sequence change creates a premature translational stop signal (p.Gly1454Glufs*94) in the COL4A5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL4A5 are known to be pathogenic (PMID: 9195222, 10752524, 14514738, 24854265, 26809805). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with COL4A5-related conditions (PMID: 34008892). |