Submissions for variant NM_033380.3(COL4A5):c.3704G>T (p.Gly1235Val)

dbSNP: rs2068130178

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV001252965	SCV001427131	likely pathogenic	X-linked Alport syndrome	2018-07-17	criteria provided, single submitter	clinical testing	A heterozygous missense variant, NM_000495.4(COL4A5):c.3704G>T, has been identified in exon 41 of 51 of the COL4A5 gene. The variant is predicted to result in a major amino acid change from glycine to valine at position 1235 of the protein (NP_000486.1(COL4A5):p.(Gly1235Val)). The glycine residue at this position has very high conservation (100 vertebrates, UCSC), and is located within the collagen triple helix repeat 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. Based on the information available at the time of curation, this variant has been classified as LIKELY PATHOGENIC.
GeneDx	RCV002508300	SCV002817831	pathogenic	not provided	2022-07-06	criteria provided, single submitter	clinical testing	Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL4A5 gene, where the majority of pathogenic missense variants occur, and is predicted to disrupt normal protein folding and function (Stenson et al., 2014; Jais et al., 2000); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24077912, 10752524, 32939031)