ClinVar Miner

Submissions for variant NM_019892.6(INPP5E):c.1754G>A (p.Arg585His) (rs752300607)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UW Hindbrain Malformation Research Program,University of Washington RCV000201629 SCV000256418 pathogenic Joubert syndrome 2015-02-23 criteria provided, single submitter research
Invitae RCV000201629 SCV001560976 uncertain significance Joubert syndrome 2020-08-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 585 of the INPP5E protein (p.Arg585His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs752300607, ExAC 0.1%). This variant has been observed in individual(s) with clinical features of Joubert syndrome (PMID: 26092869). ClinVar contains an entry for this variant (Variation ID: 217657). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). This variant disrupts the p.Arg585 amino acid residue in INPP5E. Other variant(s) that disrupt this residue have been observed in individuals with INPP5E-related conditions (PMID:23386033, 28559085), which suggests that this may be a clinically significant amino acid residue. 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.
Ocular Genomics Institute, Massachusetts Eye and Ear RCV001376233 SCV001573305 likely pathogenic Rod-cone dystrophy 2021-04-08 criteria provided, single submitter research The INPP5E c.1754G>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2, PP3, PM1, PM3. Based on this evidence we have classified this variant as Likely Pathogenic.

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