ClinVar Miner

Submissions for variant NM_005592.4(MUSK):c.2572C>T (p.Arg858Cys)

gnomAD frequency: 0.00002  dbSNP: rs200450921
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001330095 SCV001521694 uncertain significance Congenital myasthenic syndrome 9 2019-12-09 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV001751643 SCV001986423 uncertain significance not provided 2020-10-30 criteria provided, single submitter clinical testing Observed in homozygous state in patient with arthrogryposis multiplex congenita; however, patient was also found to carry homozygous variant in ECEL1 (Stattin et al., 2018); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29663639)
Invitae RCV001863214 SCV002209930 uncertain significance Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 9 2022-08-19 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 858 of the MUSK protein (p.Arg858Cys). This variant is present in population databases (rs200450921, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of MUSK-related conditions (PMID: 29663639). ClinVar contains an entry for this variant (Variation ID: 1028917). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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