Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002041695 | SCV002113635 | uncertain significance | Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 9 | 2022-09-09 | 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. ClinVar contains an entry for this variant (Variation ID: 1347440). This variant has not been reported in the literature in individuals affected with MUSK-related conditions. This variant is present in population databases (rs751851038, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 642 of the MUSK protein (p.Leu642Ser). |
Ambry Genetics | RCV003164020 | SCV003884705 | uncertain significance | Inborn genetic diseases | 2023-01-10 | criteria provided, single submitter | clinical testing | The c.1925T>C (p.L642S) alteration is located in exon 14 (coding exon 14) of the MUSK gene. This alteration results from a T to C substitution at nucleotide position 1925, causing the leucine (L) at amino acid position 642 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV004536362 | SCV004118946 | uncertain significance | MUSK-related disorder | 2023-03-03 | criteria provided, single submitter | clinical testing | The MUSK c.1925T>C variant is predicted to result in the amino acid substitution p.Leu642Ser. To our knowledge, this variant has not been reported in the literature. This variant has been reported along with a second truncating variant MUSK in an individual with congenital myasthenic syndrome (Internal Data, PreventionGenetics LCC). This variant is reported in 1 of ~2412,000 alleles in gnomAD (http://gnomad.broadinstitute.org/variant/9-113550116-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |