Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001362399 | SCV001558412 | uncertain significance | not provided | 2017-07-20 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with isoleucine at codon 350 of the IKBKAP protein (p.Met350Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with IKBKAP-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
Ambry Genetics | RCV004023731 | SCV003600408 | uncertain significance | not specified | 2022-01-26 | criteria provided, single submitter | clinical testing | The c.1050G>A (p.M350I) alteration is located in exon 11 (coding exon 10) of the IKBKAP gene. This alteration results from a G to A substitution at nucleotide position 1050, causing the methionine (M) at amino acid position 350 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV000549129 | SCV001190693 | uncertain significance | Familial dysautonomia | 2019-05-20 | no assertion criteria provided | clinical testing |