ClinVar Miner

Submissions for variant NM_001005360.2(DNM2):c.1384A>G (p.Thr462Ala) (rs201575500)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000459689 SCV000410365 benign Charcot-Marie-Tooth disease, dominant intermediate B 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000331170 SCV000410366 likely benign Myopathy, centronuclear, 1 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae RCV000459689 SCV000553368 likely benign Charcot-Marie-Tooth disease, dominant intermediate B 2019-11-20 criteria provided, single submitter clinical testing
GeneDx RCV000766564 SCV000577324 uncertain significance not provided 2017-04-04 criteria provided, single submitter clinical testing The T462A variant has been previously reported as a variant of unknown significance in an individual with congenital myopathy who harbored additional variants in other neuromuscular-related genes (Savarese et al., 2014). The T462A variant is observed in 19/66618 (0.03%) alleles from individuals of European 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 missense variant in a nearby residue (R465W) has been reported in the Human Gene Mutation Database in association with centronuclear myopathy (Stenson et al., 2014). In silico analysis predicts this variant is probably damaging to the protein structure/function.
Athena Diagnostics Inc RCV000489408 SCV000613148 likely benign not specified 2016-06-10 criteria provided, single submitter clinical testing

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