Submissions for variant NM_001379270.1(CNGA1):c.1528C>T (p.Arg510Ter)

gnomAD frequency: 0.00005  dbSNP: rs199584830

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV000225417	SCV001241005	likely pathogenic	Retinal dystrophy	2018-07-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001246009	SCV001419336	pathogenic	not provided	2024-12-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg514*) in the CNGA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 177 amino acid(s) of the CNGA1 protein. This variant is present in population databases (rs199584830, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with autosomal recessive retinitis pigmentosa (PMID: 30337596). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 236443). This variant disrupts the C-terminus of the CNGA1 protein. Other variant(s) that disrupt this region (p.Arg560*, p.Arg629*, p.Arg658Aspfs*2) have been observed in individuals with CNGA1-related conditions (PMID: 7479749, 24154662, 25611614). This suggests that this may be a clinically significant region of the protein. For these reasons, this variant has been classified as Pathogenic.
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376521	SCV001573699	pathogenic	Retinitis pigmentosa 49	2021-04-08	criteria provided, single submitter	research	The CNGA1 c.1747C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PM3, PP1, PP5. Based on this evidence we have classified this variant as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV001376521	SCV002784476	pathogenic	Retinitis pigmentosa 49	2024-06-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001246009	SCV004035895	likely pathogenic	not provided	2023-09-13	criteria provided, single submitter	clinical testing	Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 177 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); This variant is associated with the following publications: (PMID: 32581362, 26306921, 30337596, 33576794, 31456290, 26582918, 36819107, 32037395, 33749171, 24077912)
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals	RCV000225417	SCV000282549	likely pathogenic	Retinal dystrophy		no assertion criteria provided	clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000505102	SCV000599103	pathogenic	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research
Sharon lab, Hadassah-Hebrew University Medical Center	RCV000505102	SCV001160993	pathogenic	Retinitis pigmentosa	2019-06-23	no assertion criteria provided	research
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV000225417	SCV005072432	pathogenic	Retinal dystrophy	2018-01-01	no assertion criteria provided	clinical testing