ClinVar Miner

Submissions for variant NM_005592.4(MUSK):c.1724T>C (p.Ile575Thr)

gnomAD frequency: 0.00002  dbSNP: rs751889864
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000414863 SCV000493033 likely pathogenic Respiratory insufficiency; Stridor; Bilateral ptosis; Delayed gross motor development 2014-06-06 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000170588 SCV001369340 likely pathogenic Fetal akinesia deformation sequence 1 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic.
Invitae RCV002515221 SCV003440940 pathogenic Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 9 2023-12-10 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 575 of the MUSK protein (p.Ile575Thr). This variant is present in population databases (rs751889864, gnomAD 0.003%). This missense change has been observed in individuals with fetal akinesia deformation sequence (PMID: 25537362, 31974414). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 190467). 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 with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000170588 SCV000223140 pathogenic Fetal akinesia deformation sequence 1 2014-12-24 no assertion criteria provided literature only
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV001579456 SCV001807325 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001579456 SCV001958740 pathogenic not provided no assertion criteria provided clinical testing

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