Submissions for variant NM_033380.3(COL4A5):c.1117C>T (p.Arg373Ter)

dbSNP: rs104886094

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001207646	SCV001379009	pathogenic	not provided	2023-12-21	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg373*) in the COL4A5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL4A5 are known to be pathogenic (PMID: 9195222, 10752524, 14514738, 24854265, 26809805). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with a clinical diagnosis or clinical features of Alport syndrome (PMID: 8651296, 30577881). This variant is also known as 1319C>T, R373X. ClinVar contains an entry for this variant (Variation ID: 24367). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001207646	SCV001764779	pathogenic	not provided	2022-11-15	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Adequate data is not available in large population cohorts to assess the frequency of this variant in publicly available databases; however, this variant has not been detected in presumably healthy individuals tested at GeneDx; This variant is associated with the following publications: (PMID: 25525159, 8738805, 8940267, 30577881, 33330536, 10862091, 8651296, 19965530)
Fulgent Genetics, Fulgent Genetics	RCV001831593	SCV002811571	pathogenic	X-linked Alport syndrome	2022-04-22	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003421928	SCV004118414	pathogenic	COL4A5-related condition	2023-01-20	criteria provided, single submitter	clinical testing	The COL4A5 c.1117C>T variant is predicted to result in premature protein termination (p.Arg373*). This variant was reported in individuals with Alport syndrome (Renieri et al 1996. PubMed ID: 8651296; Zhang X et al 2018. PubMed ID: 30577881). This variant was also reported in a female patient with features of COL45A-related disorders (Table 2, patient #7 Mastrangelo A et al 2020. PubMed ID: 33330536). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in COL4A5 are expected to be pathogenic. This variant is interpreted as pathogenic.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001207646	SCV001977945	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001207646	SCV001979686	pathogenic	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001831593	SCV002081378	pathogenic	X-linked Alport syndrome	2021-07-23	no assertion criteria provided	clinical testing