ClinVar Miner

Submissions for variant NM_001103.4(ACTN2):c.1181G>A (p.Arg394Gln)

gnomAD frequency: 0.00001  dbSNP: rs758358941
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000548861 SCV000636927 uncertain significance Dilated cardiomyopathy 1AA; Primary familial hypertrophic cardiomyopathy 2023-06-21 criteria provided, single submitter clinical testing This variant is present in population databases (rs758358941, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 394 of the ACTN2 protein (p.Arg394Gln). This variant has not been reported in the literature in individuals affected with ACTN2-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ACTN2 protein function. ClinVar contains an entry for this variant (Variation ID: 463188).
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000768735 SCV000900105 uncertain significance Cardiomyopathy 2016-07-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV004992331 SCV005551711 uncertain significance Cardiovascular phenotype 2024-08-05 criteria provided, single submitter clinical testing The c.1181G>A (p.R394Q) alteration is located in exon 11 (coding exon 11) of the ACTN2 gene. This alteration results from a G to A substitution at nucleotide position 1181, causing the arginine (R) at amino acid position 394 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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