Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV002255754 | SCV002526549 | likely pathogenic | not provided | 2022-06-17 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (gnomAD); 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: 31130378) |
Broad Center for Mendelian Genomics, |
RCV003094188 | SCV003761239 | uncertain significance | Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome | 2023-01-25 | criteria provided, single submitter | curation | The heterozygous p.Pro479Ser variant in MSTO1 was identified by our study, in the compound heterozygous state with another variant of uncertain significance (ClinVar Variation ID: 590277) in one individual with congenital myopathy. Trio exome analysis revealed that this variant was in trans with another variant of uncertain significance (ClinVar Variation ID: 590277). The p.Pro479Ser variant in MSTO1 has been previously reported in one individual with autosomal recessive MSTO1-related muscular dystrophy (PMID: 31130378). This variant was absent from large population studies. The affected individual reported and the individual identified by our study were compound heterozygotes that carried variants of uncertain significance in trans (PMID: 31130378, ClinVar Variation ID: 590277), which increases the likelihood that p.Pro479Ser variant is pathogenic. This variant has also been reported in ClinVar (Variation ID:1691765) and has been interpreted as likely pathogenic by GeneDx. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Pro479Ser variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PM3_Supporting (Richards 2015). |