Submissions for variant NM_001379270.1(CNGA1):c.640C>T (p.Arg214Ter)

gnomAD frequency: 0.00010  dbSNP: rs759781200

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Mendelics	RCV000987444	SCV001136734	pathogenic	Retinitis pigmentosa	2019-05-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001054103	SCV001218399	pathogenic	not provided	2024-10-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg218*) in the CNGA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 473 amino acid(s) of the CNGA1 protein. This variant is present in population databases (rs759781200, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 25326637, 29785639). ClinVar contains an entry for this variant (Variation ID: 242520). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the CNGA1 protein in which other variant(s) (p.Arg424*, p.Arg493*) have been determined to be pathogenic (PMID: 26496393). 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.
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376331	SCV001573439	pathogenic	Retinitis pigmentosa 49	2021-04-08	criteria provided, single submitter	research	The CNGA1 c.859C>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. Based on this evidence we have classified this variant as Pathogenic.
DASA	RCV001376331	SCV002588784	pathogenic	Retinitis pigmentosa 49	2022-11-03	criteria provided, single submitter	clinical testing	The c.652C>T;p.Arg218* variant creates a premature translational stop signal in the CNGA1 gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 242520; PMID: 25326637, PMID: 29785639) - PS4. The variant is present at low allele frequencies population databases (rs759781200 – gnomAD 0.0005714%; ABraOM 0.000427 frequency - https://abraom.ib.usp.br/) - PM2_supporting. In summary, the currently available evidence indicates that the variant is pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV001376331	SCV005665298	pathogenic	Retinitis pigmentosa 49	2024-05-19	criteria provided, single submitter	clinical testing
Sharon lab, Hadassah-Hebrew University Medical Center	RCV000987444	SCV001160996	pathogenic	Retinitis pigmentosa	2019-06-23	no assertion criteria provided	research
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004816449	SCV005069598	pathogenic	Retinal dystrophy	2019-01-01	no assertion criteria provided	clinical testing