Submissions for variant NM_033380.3(COL4A5):c.1894G>A (p.Gly632Ser)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Servicio Canario de Salud, Hospital Universitario Nuestra Sra. de Candelaria	RCV004703374	SCV005201129	likely pathogenic	X-linked Alport syndrome	2024-09-10	criteria provided, single submitter	clinical testing	The c.1894G>A, p.(Gly632Ser) COL4A5 variant has been reported in our laboratory in a 34-year-old female patient with a clinical diagnosis of proteinuria at age 10 and kidney biopsy at age 18 compatible with focal and segmental hyalinosis. This variant has never been reported in COL4A5 related-disorders. The same variant has been identified in his 8-year-old daughter in nephrological follow-up for hematuria and albuminuria, and in his 58-year-old asymptomatic mother with hematuria. In addition, the variants c.1895G>T, p.(Gly632Val) (ClinVar Id: 2138697) have been reported as pathogenic and c.1895G>A, p.(Gly632Asp) (ClinVar Id: 2684109) as probably pathogenic/pathogenic, both affecting to the same amino acid. Most pathogenic variants in COL4A5 affect a glycine residue in the conserved Gly-Xaa-Yaa repeat sequence in the triple helix domain. This variant was absent from large population studies (gnomAD no frequency). In summary, the available evidence for c.1894G>A, p.(Gly632Ser) COL4A5 variant meets our criteria to be classified as Likely Pathogenic based upon its absence from controls and the clinical correlation in this family´s phenotype.