ClinVar Miner

Submissions for variant NM_000541.5(SAG):c.577C>T (p.Arg193Ter)

gnomAD frequency: 0.00020  dbSNP: rs201153410
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001040357 SCV001203925 pathogenic not provided 2023-11-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg193*) in the SAG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SAG are known to be pathogenic (PMID: 9452120, 15234147, 22665972). This variant is present in population databases (rs201153410, gnomAD 0.04%). This premature translational stop signal has been observed in individual(s) with Oguchi disease (PMID: 9452120, 22419846). 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: 41895). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001073952 SCV001239517 pathogenic Retinal dystrophy 2018-07-30 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001040357 SCV001250150 pathogenic not provided 2018-11-01 criteria provided, single submitter clinical testing
Medical Molecular Genetics Department, National Research Center RCV001270292 SCV001338797 pathogenic Oguchi disease-2 2019-12-01 criteria provided, single submitter clinical testing
GeneDx RCV001040357 SCV001981974 pathogenic not provided 2021-09-20 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; Observed with a deletion variant on the opposite allele (in trans) in a patient with Oguchi disease in published literature (Huang et al., 2012); This variant is associated with the following publications: (PMID: 15295660, 24265693, 25525159, 9452120, 25307992, 22419846, 21922265, 21151602, 17070587, 31054281, 31980526, 31589614)
Revvity Omics, Revvity RCV001040357 SCV002019983 pathogenic not provided 2019-08-19 criteria provided, single submitter clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002272037 SCV002557329 pathogenic Oguchi disease-1 2022-02-02 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Oguchi disease-1 (MIM#258100) and retinitis pigmentosa 47 (MIM#613758). (I) 0106 - This gene is associated with autosomal recessive disease. Autosomal dominant retinitis pigmentosa has also been reported as a founder mutation (PMID: 33047631). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (42 heterozygotes, 0 homozygotes). (SP) 0702 - Other NMD predicted variants comparable to the one identified in this case have strong previous evidence for pathogenicity (ClinVar). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in both homozygous and compound heterozygous state in individuals with Oguchi disease (ClinVar, PMID: 9452120, 22419846). It has also been reported in individuals with retinitis pigmentosa (PMID: 21151602). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Fulgent Genetics, Fulgent Genetics RCV002477062 SCV002778943 pathogenic Retinitis pigmentosa 47; Oguchi disease-1 2021-11-05 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV003224859 SCV003921003 pathogenic Retinitis pigmentosa 47 2023-03-15 criteria provided, single submitter clinical testing This variant was identified as compound heterozygous with NM_000541.5:c.733G>A._x000D_ Criteria applied: PVS1, PM2_SUP, PM3_SUP
OMIM RCV000034821 SCV000058383 pathogenic Oguchi disease 1998-01-01 no assertion criteria provided literature only

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