Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV004720613 | SCV005329303 | uncertain significance | Actin accumulation myopathy | 2023-05-20 | criteria provided, single submitter | clinical testing | The missense c.299C>A (p.Pro100His) variant in the ACTA1 gene which is located in a mutational hot spot has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is absent in gnomAD Exomes. The amino acid Proline at position 100 is changed to a Histidine changing protein sequence and it might alter its composition and physico-chemical properties. Multiple lines of computational evidence (Polyphen - Damaging, SIFT - Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The amino acid change p.Pro100His in ACTA1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. |