Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV004813085 | SCV005438645 | likely pathogenic | Alpha-actinopathy | 2024-08-07 | reviewed by expert panel | curation | The c.435C>A (p.Tyr145Ter) variant in ACTA1 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 3/7 is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism for autosomal recessive nemaline myopathy (PVS1). The highest population filtering allele frequency in gnomAD v4.1.0 is 0.000002480 (4/1179732 alleles) in the European (non-Finnish) population (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive alpha-actinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: PVS1, PM2_P. (Congenital Myopathies VCEP specifications version 1; 08/07/2024) |
| Gene |
RCV000261100 | SCV000330814 | likely pathogenic | not provided | 2019-05-28 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV001814140 | SCV002061690 | likely pathogenic | Actin accumulation myopathy; Congenital myopathy with fiber type disproportion; Progressive scapulohumeroperoneal distal myopathy | 2021-11-05 | criteria provided, single submitter | clinical testing | PVS1, PM2 |
| Labcorp Genetics |
RCV002519066 | SCV003295770 | pathogenic | Actin accumulation myopathy | 2022-02-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 280863). This premature translational stop signal has been observed in individual(s) with autosomal recessive ACTA1-related conditions (PMID: 19562689). This variant is present in population databases (rs371410845, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Tyr145*) in the ACTA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACTA1 are known to be pathogenic (PMID: 19562689). |