Submissions for variant NM_005159.5(ACTC1):c.908G>T (p.Gly303Val)

dbSNP: rs1057518530

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000412795	SCV000492264	uncertain significance	not specified	2016-12-05	criteria provided, single submitter	clinical testing	The G303V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although the G303V variant is a conservative amino acid substitution, this substitution occurs at a position that is highly conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nonetheless, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, all of which would further clarify pathogenicity.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. This result cannot be interpreted for diagnosis or used for family member screening at this time.
Invitae	RCV002521434	SCV003260904	uncertain significance	Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5	2022-07-12	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 373651). This variant has not been reported in the literature in individuals affected with ACTC1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 303 of the ACTC1 protein (p.Gly303Val).