ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.4991C>T (p.Thr1664Met)

gnomAD frequency: 0.00006  dbSNP: rs780829334
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000585445 SCV000590283 uncertain significance not provided 2019-04-30 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31918855)
CeGaT Center for Human Genetics Tuebingen RCV000585445 SCV000693254 uncertain significance not provided 2017-08-01 criteria provided, single submitter clinical testing
Invitae RCV000649125 SCV000770950 likely benign Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2024-01-02 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV001262958 SCV001441017 uncertain significance Hypertrophic cardiomyopathy 26 2019-01-01 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000585445 SCV001714857 uncertain significance not provided 2020-08-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV002350109 SCV002645667 uncertain significance Cardiovascular phenotype 2022-11-09 criteria provided, single submitter clinical testing The p.T1664M variant (also known as c.4991C>T), located in coding exon 30 of the FLNC gene, results from a C to T substitution at nucleotide position 4991. The threonine at codon 1664 is replaced by methionine, an amino acid with similar properties. This variant has been detected in individuals from dilated cardiomyopathy and left ventricular noncompaction cohorts; however, clinical details were limited, and other genetic variants were detected in the latter case (Liu S et al. Int J Cardiol. 2020 03;302:117-123; Mori V et al. Int J Cardiol Heart Vasc. 2022 Jun;40:101023). This variant was also detected in an individual from a suspected drug-induced arrhythmia and sudden death cohort, and in an individual with short stature, brachydactyly, intellectual and developmental disability and seizures syndrome who also had a mutation in the PRMT7 gene and reportedly normal echocardiogram (Martinez-Matilla M et al. Forensic Sci Int Genet, 2019 09;42:203-212; Agolini E et al. Clin. Genet., 2018 03;93:675-681). This amino acid position is highly conserved in available vertebrate species. 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.
Revvity Omics, Revvity RCV000585445 SCV003833159 uncertain significance not provided 2019-10-09 criteria provided, single submitter clinical testing

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