ClinVar Miner

Submissions for variant NM_019892.6(INPP5E):c.907G>T (p.Val303Leu)

dbSNP: rs746212325
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ocular Genomics Institute, Massachusetts Eye and Ear RCV001376481 SCV001573638 uncertain significance Rod-cone dystrophy 2021-04-08 criteria provided, single submitter research The INPP5E c.907G>T 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. Based on this evidence we have classified this variant as Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001865904 SCV002132001 uncertain significance Familial aplasia of the vermis 2022-10-13 criteria provided, single submitter clinical testing 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. This variant disrupts the p.Val303 amino acid residue in INPP5E. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23386033, 26092869). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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) performed at Invitae indicates that this missense variant is expected to disrupt INPP5E protein function. ClinVar contains an entry for this variant (Variation ID: 1065767). This missense change has been observed in individual(s) with clinical features of Joubert syndrome (Invitae). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 303 of the INPP5E protein (p.Val303Leu).

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