Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222615 | SCV002500814 | uncertain significance | not specified | 2024-05-28 | criteria provided, single submitter | clinical testing | Variant summary: MYO9A c.4550G>A (p.Arg1517His) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in MYO9A causing Myasthenic Syndrome, Congenital, 24, Presynaptic phenotype, suggesting the variant could be benign. c.4550G>A has been reported in the literature in a setting of whole exome sequencing in at least one compound heterozygous individual affected with Myasthenic Syndrome, Congenital, 24, Presynaptic with conflicting evidence for pathogenicity (e.g. O'Connor_2016). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 590980). The following publications have been ascertained in the context of this evaluation (PMID: 30237576, 27259756). Based on the evidence outlined above, the variant was classified as VUS-possibly benign. |
| OMIM | RCV000722150 | SCV000854567 | pathogenic | Myasthenic syndrome, congenital, 24, presynaptic | 2018-11-29 | no assertion criteria provided | literature only |