ClinVar Miner

Submissions for variant NM_003383.5(VLDLR):c.1838G>A (p.Arg613His) (rs35948251)

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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 RCV000193084 SCV000249380 uncertain significance not specified 2015-01-07 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000359068 SCV000479355 uncertain significance Congenital cerebellar hypoplasia 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000658403 SCV000780175 uncertain significance not provided 2018-05-30 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the VLDLR gene. The R613H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is observed in 28/126434 (0.02%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). The R613H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV001168790 SCV001331411 uncertain significance Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 1 2018-01-13 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.

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