ClinVar Miner

Submissions for variant NM_005045.4(RELN):c.8863C>T (p.Arg2955Cys) (rs114501042)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000657945 SCV000231370 uncertain significance not provided 2018-08-10 criteria provided, single submitter clinical testing
Invitae RCV001079326 SCV000656369 likely benign Norman-Roberts syndrome; Epilepsy, familial temporal lobe, 7 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000657945 SCV000779715 uncertain significance not provided 2018-05-21 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the RELN gene. The R2955C 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 80/18854 (0.4%) alleles from individuals of East Asian background in large population cohorts (Lek et al., 2016). The R2955C 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 analyses, including protein predictors and evolutionary conservation, support that this variant does not alter 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.
Illumina Clinical Services Laboratory,Illumina RCV001161856 SCV001323766 likely benign Norman-Roberts syndrome 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

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