ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.21341G>A (p.Arg7114Gln) (rs372284984)

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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 RCV000530441 SCV000416853 uncertain significance Nemaline myopathy 2 2018-01-12 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.
GeneDx RCV000519243 SCV000621755 uncertain significance not specified 2017-10-25 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NEB gene. The R7114Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R7114Q variant is observed in 9/18854 (0.5%) alleles from individuals of East Asian background (Lek et al., 2016). The R7114Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the 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.
Invitae RCV000530441 SCV000640681 uncertain significance Nemaline myopathy 2 2019-10-02 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 7114 of the NEB protein (p.Arg7114Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs372284984, ExAC 0.07%). This variant has not been reported in the literature in individuals with NEB-related disease. ClinVar contains an entry for this variant (Variation ID: 331426). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. RCV000530441 SCV001460600 uncertain significance Nemaline myopathy 2 2020-01-17 no assertion criteria provided clinical testing

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