Submissions for variant NM_000440.3(PDE6A):c.1957C>T (p.Arg653Ter)

gnomAD frequency: 0.00001  dbSNP: rs753942596

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000622936	SCV000742668	pathogenic	Inborn genetic diseases	2017-06-16	criteria provided, single submitter	clinical testing
GeneDx	RCV000627204	SCV000748191	pathogenic	not provided	2018-01-26	criteria provided, single submitter	clinical testing	The R653X variant has been published as a homozygous pathogenic variant in a patient diagnosed with autosomal recessive retinitis pigmentosa (Perez-Carro et al., 2016). The R653X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The R653X nonsense variant in the PDE6A gene is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. This variant is interpreted to be pathogenic.
Mendelics	RCV000504732	SCV001136999	pathogenic	Retinitis pigmentosa	2019-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000627204	SCV001249585	pathogenic	not provided	2016-09-01	criteria provided, single submitter	clinical testing
Invitae	RCV000627204	SCV001403249	pathogenic	not provided	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg653*) in the PDE6A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PDE6A are known to be pathogenic (PMID: 7493036, 22128245, 23847139). This variant is present in population databases (rs753942596, gnomAD 0.009%). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 26806561, 29693493, 30619975). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 437983). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000627204	SCV001446816	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel	RCV000504732	SCV004030432	pathogenic	Retinitis pigmentosa	2023-07-24	criteria provided, single submitter	research	Clinical significance based on ACMG v2.0
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504732	SCV000598726	likely pathogenic	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research
Sharon lab, Hadassah-Hebrew University Medical Center	RCV000504732	SCV001161178	pathogenic	Retinitis pigmentosa	2019-06-23	no assertion criteria provided	research