Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001050112 | SCV001214204 | uncertain significance | Branched-chain keto acid dehydrogenase kinase deficiency | 2019-01-28 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BCKDK-related conditions. This variant is present in population databases (rs371078966, ExAC 0.003%). This sequence change replaces threonine with isoleucine at codon 284 of the BCKDK protein (p.Thr284Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. |
| Ambry Genetics | RCV002553724 | SCV003526262 | uncertain significance | Inborn genetic diseases | 2021-07-13 | criteria provided, single submitter | clinical testing | The c.851C>T (p.T284I) alteration is located in exon 10 (coding exon 9) of the BCKDK gene. This alteration results from a C to T substitution at nucleotide position 851, causing the threonine (T) at amino acid position 284 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |