Submissions for variant NM_001142800.2(EYS):c.9036del (p.Leu3013fs)

dbSNP: rs1225304963

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000802365	SCV000942191	pathogenic	not provided	2024-01-21	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu3013Serfs*6) in the EYS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 132 amino acid(s) of the EYS protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 27735924, 29159838). ClinVar contains an entry for this variant (Variation ID: 647784). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the EYS protein in which other variant(s) (p.Val3096Leufs*28) have been determined to be pathogenic (PMID: 24474277, 26261414, 29550188). 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.
Revvity Omics, Revvity	RCV001784421	SCV002022256	pathogenic	Retinitis pigmentosa 25	2021-02-06	criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV001784421	SCV002766719	pathogenic	Retinitis pigmentosa 25	2020-05-26	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0205 - Variant is predicted to result in a truncated protein with less than 1/3 of the protein affected (exon 43 of 43). (P) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0600 - Variant is located in an annotated domain or motif and truncation will result in loss of part of the laminin G domain (NCBI, Decipher, PDB). (N) 0701 - Comparable variants have very strong previous evidence for pathogenicity. Other variants predicted to cause a truncated protein have been reported as pathogenic in individuals with retinitis pigmentosa (ClinVar, Decipher). (P) 0803 - Low previous evidence of pathogenicity in unrelated individuals. The variant has been previously reported in patients with EYS-related retinal dystrophy (ClinVar, PMID: 31074760). (P) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign
CeGaT Center for Human Genetics Tuebingen	RCV000802365	SCV003917072	pathogenic	not provided	2023-04-01	criteria provided, single submitter	clinical testing	EYS: PM3:Strong, PVS1:Strong, PM2, PP4
Baylor Genetics	RCV001784421	SCV004192880	pathogenic	Retinitis pigmentosa 25	2023-10-19	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001784421	SCV002083465	pathogenic	Retinitis pigmentosa 25	2020-09-11	no assertion criteria provided	clinical testing