ClinVar Miner

Submissions for variant NM_006096.3(NDRG1):c.431A>G (p.Tyr144Cys) (rs139220402)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235434 SCV000293911 uncertain significance not provided 2016-02-17 criteria provided, single submitter clinical testing The Y144C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The Y144C 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. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001071546 SCV001236854 uncertain significance Charcot-Marie-Tooth disease type 4 2019-12-06 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 144 of the NDRG1 protein (p.Tyr144Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs139220402, ExAC 0.01%). This variant has not been reported in the literature in individuals with NDRG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 246379). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; 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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