ClinVar Miner

Submissions for variant NM_001458.4(FLNC):c.2450T>C (p.Ile817Thr) (rs200653747)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000541682 SCV000650949 uncertain significance Myofibrillar myopathy, filamin C-related; Myopathy, distal, 4; Cardiomyopathy, familial hypertrophic, 26; Dilated Cardiomyopathy, Dominant 2018-05-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 817 of the FLNC protein (p.Ile817Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs200653747, ExAC 0.01%). This variant has been observed in an individual affected with hypertrophic cardiomyopathy (PMID: 29030401). ClinVar contains an entry for this variant (Variation ID: 228692). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Laboratory for Molecular Medicine,Partners HealthCare 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.

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