Submissions for variant NM_033380.3(COL4A5):c.4994+1G>A

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003684807	SCV004406357	pathogenic	not provided	2022-10-13	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the COL4A5 protein in which other variant(s) (p.Arg1677*) have been determined to be pathogenic (PMID: 10094548, 12796257, 19728970, 19965530). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with COL4A5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 50 of the COL4A5 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.
Watson Genetic Lab	RCV003985630	SCV004801095	pathogenic	X-linked Alport syndrome	2022-07-25	criteria provided, single submitter	clinical testing	ACMG Guideline scores: PVS1, PM2, PP1
Fulgent Genetics, Fulgent Genetics	RCV003985630	SCV005683218	likely pathogenic	X-linked Alport syndrome	2024-02-09	criteria provided, single submitter	clinical testing