Submissions for variant NM_001100.3(ACTA1):c.478G>A (p.Gly160Ser) (rs1064794652)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486223	SCV000569651	likely pathogenic	not provided	2016-03-15	criteria provided, single submitter	clinical testing	The G160S variant in the ACTA1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. However, a missense pathogenic variant at this same codon (G160C), as well as missense pathogenic variants in neighboring codons (D156N, H163D, V165L, V165M), have been reported in the Human Gene Mutation Database in association with ACTA1-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. The G160S variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G160S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The G160S variant is a strong candidate for a pathogenic variant.
Baylor Miraca Genetics Laboratories,	RCV000679902	SCV000807333	uncertain significance	Nemaline myopathy 3	2017-09-01	criteria provided, single submitter	clinical testing	At the time of reporting, this mutation was novel, but different substitutions of the same amino acid have been described. Likely pathogenicity based on de novo finding in a newborn female with fetal akinesia, extreme hypotonia, absent movement and respiratory effort, dysmorphic features, and osteopenia