ClinVar Miner

Submissions for variant NM_006096.3(NDRG1):c.1022G>A (p.Arg341His) (rs1392179290)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520826 SCV000621378 uncertain significance not provided 2017-10-04 criteria provided, single submitter clinical testing The R341H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R341H variant is not observed in large population cohorts (Lek et al., 2016). This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the R341H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000685216 SCV000812689 uncertain significance Charcot-Marie-Tooth disease type 4 2018-04-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 341 of the NDRG1 protein (p.Arg341His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NDRG1-related disease. ClinVar contains an entry for this variant (Variation ID: 452561). 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 C0"). 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.

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