Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute Of Human Genetics Munich, |
RCV000021288 | SCV001150057 | pathogenic | X-linked Alport syndrome | 2019-02-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001851987 | SCV002307144 | likely pathogenic | not provided | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 475 of the COL4A5 protein (p.Gly475Ser). This variant also falls at the last nucleotide of exon 21, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of Alport syndrome (PMID: 20378821; Invitae). ClinVar contains an entry for this variant (Variation ID: 24409). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change is associated with inconclusive levels of altered splicing (PMID: 35005319). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |