ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.1616C>T (p.Pro539Leu)

gnomAD frequency: 0.00009  dbSNP: rs375570393
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000804565 SCV000944481 likely benign Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2024-01-29 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001726333 SCV001962095 likely benign not provided 2021-09-01 criteria provided, single submitter clinical testing
GeneDx RCV001726333 SCV001989846 uncertain significance not provided 2019-05-17 criteria provided, single submitter clinical testing Reported in 1/307 healthy Chinese control individuals (Cui et al., 2018), although family history and segregation studies were not reported; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30411535)
Ambry Genetics RCV002397632 SCV002705337 uncertain significance Cardiovascular phenotype 2021-04-30 criteria provided, single submitter clinical testing The p.P539L variant (also known as c.1616C>T), located in coding exon 10 of the FLNC gene, results from a C to T substitution at nucleotide position 1616. The proline at codon 539 is replaced by leucine, an amino acid with similar properties. This variant was detected in an individual with exercise-related sudden cardiac arrest (Asatryan B et al. Am J Cardiol, 2019 06;123:2031-2038), and in a healthy control in a hypertrophic cardiomyopathy (HCM) cohort (Cui H et al. Mol Genet Genomic Med, 2018 11;6:1104-1113). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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