Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001299150 | SCV001488229 | uncertain significance | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 9 | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with aspartic acid at codon 427 of the MUSK protein (p.His427Asp). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and aspartic acid. This variant is present in population databases (rs751266636, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with MUSK-related conditions. 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. 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 | RCV003284147 | SCV003954625 | uncertain significance | Inborn genetic diseases | 2023-03-31 | criteria provided, single submitter | clinical testing | The c.1279C>G (p.H427D) alteration is located in exon 10 (coding exon 10) of the MUSK gene. This alteration results from a C to G substitution at nucleotide position 1279, causing the histidine (H) at amino acid position 427 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |