ClinVar Miner

Submissions for variant NM_000322.5(PRPH2):c.587T>A (p.Ile196Asn)

dbSNP: rs1131691378
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493047 SCV000582002 likely pathogenic not provided 2015-08-18 criteria provided, single submitter clinical testing The I196N variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The I196N variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The I196N variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (D194E, R195G, R195L, R195Q, K197E, S198R, N199D, V200E) have been reported in the Human Gene Mutation Database in association with PRPH2-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, based on the currently available information, the I196N variant is a candidate for a disease-causing variant although the possibility that it is a benign polymorphism cannot be completely excluded
NEI Ophthalmic Genomics Laboratory, National Institutes of Health RCV001250277 SCV001424589 likely pathogenic Cone-rod dystrophy 2020-01-07 criteria provided, single submitter clinical testing The variant NM_000322.4:c.587T>A in the PRPH2 gene has not been reported to our knowledge . We found this variant in 1 patient(s) in a PRPH2 cohort study (Reeves et al. 2020). This variant is not listed in dbSNP and/or HGMD. It is absent in gnomAD browser. It is not enriched in the PRPH2 disease cohort. We invoked ACMG criteria [PM1, PM2, PP5, PP3] and classified NM_000322.4:c.587T>A in the PRPH2 gene as a Likely Pathogenic mutation.
Leiden Open Variation Database RCV000493047 SCV001745158 likely pathogenic not provided 2021-04-06 no assertion criteria provided curation Curator: Global Variome, with Curator vacancy. Submitter to LOVD: Manon Peeters.

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