Total submissions: 2
| 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. |