Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000418492 | SCV000511961 | uncertain significance | not provided | 2022-12-12 | criteria provided, single submitter | clinical testing | Reported in association with HCM (Wang et al., 2014; Murphy et al., 2016); Not observed at significant frequency 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: 25132132, 26914223, 26582918, 27535533) |
Invitae | RCV000699207 | SCV000827907 | uncertain significance | Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 | 2020-11-18 | 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). This variant has been observed in several individuals affected with hypertrophic cardiomyopathy (PMID: 25132132, 26914223). ClinVar contains an entry for this variant (Variation ID: 377435). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with glutamine at codon 103 of the ACTC1 protein (p.His103Gln). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and glutamine. |