ClinVar Miner

Submissions for variant NM_019892.6(INPP5E):c.1732G>A (p.Gly578Arg)

gnomAD frequency: 0.00002  dbSNP: rs559636009
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000194100 SCV000247608 uncertain significance not specified 2014-05-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001206813 SCV001378142 uncertain significance Familial aplasia of the vermis 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 578 of the INPP5E protein (p.Gly578Arg). This variant is present in population databases (rs559636009, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with INPP5E-related conditions. ClinVar contains an entry for this variant (Variation ID: 211184). 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. 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.
GeneDx RCV004725046 SCV005333534 uncertain significance not provided 2023-04-17 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23386033)
PreventionGenetics, part of Exact Sciences RCV004528980 SCV004109232 uncertain significance INPP5E-related disorder 2024-05-29 no assertion criteria provided clinical testing The INPP5E c.1732G>A variant is predicted to result in the amino acid substitution p.Gly578Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.035% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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