ClinVar Miner

Submissions for variant NM_006096.4(NDRG1):c.634C>T (p.Arg212Cys)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV001159105 SCV001320793 uncertain significance Charcot-Marie-Tooth disease, type 4D 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.
Molecular Genetics Laboratory,London Health Sciences Centre RCV001173717 SCV001336831 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Invitae RCV001246999 SCV001420395 uncertain significance Charcot-Marie-Tooth disease type 4 2019-09-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 212 of the NDRG1 protein (p.Arg212Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs138285479, ExAC 0.2%). This variant has not been reported in the literature in individuals with NDRG1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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 RCV001655688 SCV001871320 uncertain significance not provided 2021-08-05 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533)

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