ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.4651G>A (p.Ala1551Thr)

gnomAD frequency: 0.00008  dbSNP: rs565918031
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000649169 SCV000770994 likely benign Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2024-01-14 criteria provided, single submitter clinical testing
GeneDx RCV001574184 SCV001800952 likely benign not provided 2021-02-24 criteria provided, single submitter clinical testing Identified in association with frontotemporal dementia (Janssens et al., 2015) and hypertrophic cardiomyopathy (Jaafar et al., 2016) in published literature; Reported as a variant of uncertain significance by another clinical laboratory in ClinVar (ClinVar Variant ID# 539435; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26555887, 27574918, 32936277)
Ambry Genetics RCV002331237 SCV002633699 uncertain significance Cardiovascular phenotype 2022-06-06 criteria provided, single submitter clinical testing The p.A1551T variant (also known as c.4651G>A), located in coding exon 27 of the FLNC gene, results from a G to A substitution at nucleotide position 4651. The alanine at codon 1551 is replaced by threonine, an amino acid with similar properties. This variant has been detected in an individual with hypertrophic cardiomyopathy, and has also been detected in an individual with frontotemporal dementia (Janssens J et al. Acta Neuropathol Commun, 2015;3:68; Jaafar N et al. Genet Test Mol Biomarkers. 2016;20:674-679). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV001574184 SCV003833161 uncertain significance not provided 2022-09-26 criteria provided, single submitter clinical testing

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