ClinVar Miner

Submissions for variant NM_005159.5(ACTC1):c.1085A>C (p.Gln362Pro)

gnomAD frequency: 0.00001  dbSNP: rs375435815
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001882383 SCV002160666 uncertain significance Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 2021-11-24 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with ACTC1-related conditions. This variant is present in population databases (rs375435815, gnomAD 0.0009%). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 362 of the ACTC1 protein (p.Gln362Pro).
Ambry Genetics RCV002422986 SCV002724902 uncertain significance Cardiovascular phenotype 2021-08-07 criteria provided, single submitter clinical testing The p.Q362P variant (also known as c.1085A>C), located in coding exon 6 of the ACTC1 gene, results from an A to C substitution at nucleotide position 1085. The glutamine at codon 362 is replaced by proline, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV001882383 SCV002779398 uncertain significance Hypertrophic cardiomyopathy 11; Dilated cardiomyopathy 1R; Atrial septal defect 5 2022-05-25 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004010789 SCV004844802 uncertain significance Hypertrophic cardiomyopathy 2023-12-01 criteria provided, single submitter clinical testing This missense variant replaces glutamine with proline at codon 362 of the ACTC1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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