Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV001251478 | SCV001427107 | likely pathogenic | X-linked Alport syndrome | 2018-05-23 | criteria provided, single submitter | clinical testing | A heterozygous missense variant, NM_000495.4(COL4A5):c.1225G>A, has been identified in exon 20 of 51 of the COL4A5 gene. The variant is predicted to result in a minor amino acid change from glycine to serine at position 409 of the protein (NP_000486.1(COL4A5):p.(Gly409Ser)). The glycine residue at this position has very high conservation (100 vertebrates, UCSC), and is located within the collagen triple helical functional domain. In-silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is absent in population databases (gnomAD, dbSNP, 1000G). This variant has not been previously reported in clinical cases. A different variant in the same codon resulting in a change to aspartic acid (p.Gly409Asp) has also been shown to cause Alport Syndrome (Renieri A. et al., (1996)). Based on the information available at the time of curation, this variant has been classified as LIKELY PATHOGENIC. |