Submissions for variant NM_033380.3(COL4A5):c.5038C>T (p.Arg1680Ter)

dbSNP: rs281874753

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Gharavi Laboratory, Columbia University	RCV000681926	SCV000809409	pathogenic	not provided	2018-09-16	criteria provided, single submitter	research
Institute Of Human Genetics Munich, Klinikum Rechts Der Isar, Tu München	RCV000021665	SCV001149741	pathogenic	X-linked Alport syndrome	2018-12-06	criteria provided, single submitter	clinical testing
Invitae	RCV000681926	SCV001591547	pathogenic	not provided	2023-02-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1674*) in the COL4A5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 12 amino acid(s) of the COL4A5 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Alport syndrome (PMID: 12105244, 20378821, 30577881). This variant is also known as p.Arg1680*. ClinVar contains an entry for this variant (Variation ID: 24785). 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. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000021665	SCV002813228	pathogenic	X-linked Alport syndrome	2022-02-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000681926	SCV003805508	pathogenic	not provided	2023-01-23	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation, as the last 12 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 12105244, 30577881, 20378821, 30586318)
Department of Traditional Chinese Medicine, Fujian Provincial Hospital	RCV003886366	SCV004698203	pathogenic	Alport syndrome		no assertion criteria provided	research	In a male patient with Alport syndrome, we found the mutant c.5038C>T (p.Arg1680Ter), which results in a shortened protein that causes illness. His renal pathology showed negative type IV collagen staining for alpha 3 and alpha 5, focal foamy cells in the renal interstitium, and stratified alterations in the basement membrane on electron microscopy, all of which were thought to be signs of renal damage associated with X-linked Alport syndrome. Furthermore, numerous investigations have established the pathogenicity of this mutant location (PMID: 10094548, 12796257, 19728970, 19965530).