Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000819298 | SCV000959951 | uncertain significance | Neuropathy, hereditary motor and sensory, type 6B | 2019-06-28 | 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 tolerated, 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 SLC25A46-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with asparagine at codon 193 of the SLC25A46 protein (p.Lys193Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. |