ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.2450T>C (p.Ile817Thr)

gnomAD frequency: 0.00004  dbSNP: rs200653747
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000221213 SCV000271789 uncertain significance not specified 2014-02-12 criteria provided, single submitter clinical testing The c.2450T>C variant in FLNC has not been reported in the literature nor previo usly identified by our laboratory. The c.2450T>C has been identified in 2/4306 o f African American chromosomes by the NHLBI Exome Sequencing Project (http://evs .gs.washington.edu/EVS) though this frequency is not high enough to rule out a p athogenic role given the later onset of disease. Computational analyses suggest that the Ile817Thr variant in FLNC may impact the protein, though this informati on is not predictive enough to determine pathogenicity. In summary, additional d ata is needed to determine the clinical significance of this variant.
Invitae RCV000541682 SCV000650949 likely benign Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2023-09-21 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002500712 SCV002800156 uncertain significance Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26 2021-09-06 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV002500712 SCV003919976 uncertain significance Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26 2021-03-30 criteria provided, single submitter clinical testing FLNC NM_001458.4 exon 16 p.Ile817Thr (c.2450T>C): This variant has been reported in the literature in one individual with hypertrophic cardiomyopathy (Cirino 2017 PMID:29030401). This variant is present in 0.008% (2/24146) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/7-128482908-T-C) and is present in ClinVar (Variation ID:228692). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
GeneDx RCV003441792 SCV004169629 uncertain significance not provided 2023-05-15 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in a patient with HCM who harbored a second variant in the ABCC9 gene (Cirino et al., 2017); This variant is associated with the following publications: (PMID: 32112656, 29030401)

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