ClinVar Miner

Submissions for variant NM_019892.6(INPP5E):c.1730C>G (p.Pro577Arg)

gnomAD frequency: 0.00405  dbSNP: rs147967974
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001095320 SCV000478747 uncertain significance Joubert syndrome 1 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000489191 SCV000577458 uncertain significance not provided 2017-03-29 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the INPP5E gene. The P577R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P577R variant is observed in 25/9198 (0.3%) alleles from individuals of European background, including one homozygous individual (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is not conserved, and Arginine is observed at this position in evolution. However, the P577R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000302693 SCV001000685 benign Familial aplasia of the vermis 2023-11-16 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000489191 SCV003917744 benign not provided 2023-01-01 criteria provided, single submitter clinical testing INPP5E: BS1, BS2

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.