ClinVar Miner

Submissions for variant NM_019892.6(INPP5E):c.1543C>T (p.Arg515Trp)

gnomAD frequency: 0.00001  dbSNP: rs13297509
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001851510 SCV002310730 likely pathogenic Familial aplasia of the vermis 2023-05-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 515 of the INPP5E protein (p.Arg515Trp). This variant is present in population databases (rs13297509, gnomAD 0.03%). This missense change has been observed in individuals with clinical features of Joubert syndrome or retinitis pigmentosa (PMID: 19668216, 27081510, 28559085; Invitae). ClinVar contains an entry for this variant (Variation ID: 397). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on INPP5E protein function. Experimental studies have shown that this missense change affects INPP5E function (PMID: 19668216). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000022402 SCV000043087 pathogenic Joubert syndrome 1 2009-09-01 no assertion criteria provided literature only

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