ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.217C>T (p.Arg73Trp) (rs77994592)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000536943 SCV000640693 likely benign Nemaline myopathy 2 2019-12-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001199841 SCV001370563 uncertain significance not specified 2020-05-08 criteria provided, single submitter clinical testing Variant summary: NEB c.217C>T (p.Arg73Trp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00016 in 248860 control chromosomes, predominantly at a frequency of 0.0024 within the African or African-American subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in NEB causing Nemaline Myopathy 2 (0.0024 vs 0.0035), allowing no conclusion about variant significance. c.217C>T has been reported in the literature in at least one individual affected with Limb-girdle muscular dystrophy (Brauers_2016). This report does not provide unequivocal conclusions about association of the variant with Nemaline Myopathy 2. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.

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