Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000180571 | SCV000233041 | uncertain significance | not provided | 2014-10-27 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001852253 | SCV002130623 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2021-07-04 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with isoleucine at codon 501 of the FLNC protein (p.Thr501Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. ClinVar contains an entry for this variant (Variation ID: 199068). 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: "Possibly 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. |
Ambry Genetics | RCV003278680 | SCV004004627 | uncertain significance | Cardiovascular phenotype | 2023-05-22 | criteria provided, single submitter | clinical testing | The p.T501I variant (also known as c.1502C>T), located in coding exon 9 of the FLNC gene, results from a C to T substitution at nucleotide position 1502. The threonine at codon 501 is replaced by isoleucine, an amino acid with similar properties. 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. |