Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317045 | SCV004020785 | uncertain significance | not specified | 2023-06-16 | criteria provided, single submitter | clinical testing | Variant summary: KBTBD13 c.742C>A (p.Arg248Ser) results in a non-conservative amino acid change located in the Kelch-type beta propeller domain (IPR015915) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 153572 control chromosomes in GnomAD. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.742C>A has been reported in the literature in an individual affected with features of Nemaline Myopathy 6 (Sambuughin_2010). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 21109227). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Labcorp Genetics |
RCV000024057 | SCV004374618 | uncertain significance | Nemaline myopathy 6 | 2023-11-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 248 of the KBTBD13 protein (p.Arg248Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of nemaline myopathy (PMID: 21109227). ClinVar contains an entry for this variant (Variation ID: 31063). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KBTBD13 protein function with a positive predictive value of 80%. 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. |
| Molecular Genetics, |
RCV000024057 | SCV004812850 | uncertain significance | Nemaline myopathy 6 | 2023-08-01 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000024057 | SCV000045348 | pathogenic | Nemaline myopathy 6 | 2010-12-10 | no assertion criteria provided | literature only |