ClinVar Miner

Submissions for variant NM_005592.4(MUSK):c.1061C>T (p.Thr354Met)

gnomAD frequency: 0.00010  dbSNP: rs200064775
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000695873 SCV000824397 uncertain significance Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 9 2022-08-07 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 354 of the MUSK protein (p.Thr354Met). This variant is present in population databases (rs200064775, gnomAD 0.03%). 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: 574041). 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 not 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.
GeneDx RCV001771968 SCV001991966 uncertain significance not provided 2019-04-09 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002532336 SCV003715630 uncertain significance Inborn genetic diseases 2021-11-08 criteria provided, single submitter clinical testing The c.1061C>T (p.T354M) alteration is located in exon 9 (coding exon 9) of the MUSK gene. This alteration results from a C to T substitution at nucleotide position 1061, causing the threonine (T) at amino acid position 354 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV001771968 SCV003817099 uncertain significance not provided 2019-02-06 criteria provided, single submitter clinical testing

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