ClinVar Miner

Submissions for variant NM_005592.4(MUSK):c.2002C>T (p.Arg668Cys)

gnomAD frequency: 0.00001  dbSNP: rs754730206
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000541009 SCV000656574 uncertain significance Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 9 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 668 of the MUSK protein (p.Arg668Cys). This variant is present in population databases (rs754730206, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MUSK-related conditions. ClinVar contains an entry for this variant (Variation ID: 476139). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MUSK protein function. 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 RCV004024354 SCV004935687 uncertain significance Inborn genetic diseases 2023-11-29 criteria provided, single submitter clinical testing The c.2002C>T (p.R668C) alteration is located in exon 15 (coding exon 15) of the MUSK gene. This alteration results from a C to T substitution at nucleotide position 2002, causing the arginine (R) at amino acid position 668 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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