ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.20956G>C (p.Asp6986His) (rs150874422)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000425742 SCV000536355 uncertain significance not provided 2018-08-31 criteria provided, single submitter clinical testing The D6986H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D6986H variant is observed in 15/9798 (0.15%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This 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, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with nemaline myopathy (Stenson et al., 2014).
Invitae RCV000550442 SCV000640674 uncertain significance Nemaline myopathy 2 2019-10-02 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 6986 of the NEB protein (p.Asp6986His). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is present in population databases (rs150874422, ExAC 0.2%). This variant has not been reported in the literature in individuals with NEB-related disease. ClinVar contains an entry for this variant (Variation ID: 393007). 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"; 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.
Natera, Inc. RCV000550442 SCV001460606 uncertain significance Nemaline myopathy 2 2020-01-17 no assertion criteria provided clinical testing

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