Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre for Mendelian Genomics, |
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, |
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, |
RCV001579456 | SCV001807325 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001579456 | SCV001958740 | pathogenic | not provided | no assertion criteria provided | clinical testing |