Submissions for variant NM_001142800.2(EYS):c.4045C>T (p.Arg1349Ter)

gnomAD frequency: 0.00001  dbSNP: rs930421180

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001040519	SCV001204098	pathogenic	not provided	2023-05-16	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 438197). This premature translational stop signal has been observed in individuals with retinitis pigmentosa (PMID: 24265693, 28041643). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg1349*) in the EYS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EYS are known to be pathogenic (PMID: 18836446, 20333770).
CeGaT Center for Human Genetics Tuebingen	RCV001040519	SCV001248827	pathogenic	not provided	2017-01-01	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001040519	SCV001762174	pathogenic	not provided	2021-06-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001040519	SCV001794834	pathogenic	not provided	2022-08-22	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; This variant is associated with the following publications: (PMID: 35046417, 24265693, 28041643, 30337596, 31054281, 32581362, 31589614, 31074760, 32531858)
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV001731733	SCV001984113	likely pathogenic	Retinitis pigmentosa 25	2019-12-26	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001731733	SCV004192912	pathogenic	Retinitis pigmentosa 25	2024-03-25	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000504982	SCV004242015	pathogenic	Retinitis pigmentosa	2023-12-08	criteria provided, single submitter	clinical testing	Variant summary: EYS c.4045C>T (p.Arg1349X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 3.2e-05 in 31404 control chromosomes. c.4045C>T has been reported in the literature in mulitple individuals affected with Retinitis Pigmentosa (e.g., Weisschuh_2020). The following publication have been ascertained in the context of this evaluation (PMID: 32531858). Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014; and all submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004817735	SCV005069844	pathogenic	Retinal dystrophy	2019-01-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001731733	SCV005670611	pathogenic	Retinitis pigmentosa 25	2024-06-15	criteria provided, single submitter	clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504982	SCV000599151	likely pathogenic	Retinitis pigmentosa	2015-01-01	no assertion criteria provided	research
Natera, Inc.	RCV000504982	SCV001459426	pathogenic	Retinitis pigmentosa	2020-09-16	no assertion criteria provided	clinical testing