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: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001851510 SCV002310730 likely pathogenic Familial aplasia of the vermis 2024-09-02 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; internal data). ClinVar contains an entry for this variant (Variation ID: 397). Invitae Evidence 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 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.
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital RCV000022402 SCV005420857 pathogenic Joubert syndrome 1 2024-10-04 criteria provided, single submitter research PM3,PS3,PM2,PP4,PP1
Fulgent Genetics, Fulgent Genetics RCV005049303 SCV005680284 likely pathogenic MORM syndrome; Joubert syndrome 1 2024-01-15 criteria provided, single submitter clinical testing
OMIM RCV000022402 SCV000043087 pathogenic Joubert syndrome 1 2009-09-01 no assertion criteria provided literature only

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