ClinVar Miner

Submissions for variant NM_001142800.2(EYS):c.3250A>C (p.Thr1084Pro)

gnomAD frequency: 0.00049  dbSNP: rs778646190
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000176282 SCV000227913 uncertain significance not provided 2015-01-20 criteria provided, single submitter clinical testing
Counsyl RCV000673072 SCV000798240 uncertain significance Retinitis pigmentosa 25 2018-03-06 criteria provided, single submitter clinical testing
Mendelics RCV000673072 SCV001137165 uncertain significance Retinitis pigmentosa 25 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000176282 SCV001234833 uncertain significance not provided 2022-10-29 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1084 of the EYS protein (p.Thr1084Pro). This variant is present in population databases (rs778646190, gnomAD 0.1%). This missense change has been observed in individual(s) with retinal disease. However, this variant has frequently been identified on the same chromosome as other EYS variants, making its clinical significance uncertain (PMID: 25097241, 26667666, 29550188). ClinVar contains an entry for this variant (Variation ID: 195666). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Blueprint Genetics RCV001075858 SCV001241497 uncertain significance Retinal dystrophy 2019-08-08 criteria provided, single submitter clinical testing
GeneDx RCV000176282 SCV001774232 likely benign not provided 2019-10-08 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 26667666, 29550188, 25097241)
PreventionGenetics, part of Exact Sciences RCV003422070 SCV004117194 uncertain significance EYS-related disorder 2023-03-01 criteria provided, single submitter clinical testing The EYS c.3250A>C variant is predicted to result in the amino acid substitution p.Thr1084Pro. This variant has been reported in individuals with retinitis pigmentosa; however, in several of these cases it was determined to be on the same allele (in cis) with the pathogenic variant c.3443+1G>T as well as the uncertain missense variant c.4402G>C (p.Asp1468His) (Wang et al. 2014. PubMed ID: 25097241; Ge et al. 2015. PubMed ID: 26667666; Sengillo et al. 2018. PubMed ID: 29550188). This variant is reported in 0.15% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-65523464-T-G). Although we suspect that this variant may be benign by itself, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001277985 SCV001464970 uncertain significance Autosomal recessive retinitis pigmentosa 2020-08-31 no assertion criteria provided clinical testing

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