Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000702724 | SCV000831590 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with tyrosine at codon 824 of the FLNC protein (p.Asn824Tyr). The asparagine residue is highly conserved and there is a large physicochemical difference between asparagine and tyrosine. 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. 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV002458290 | SCV002738276 | uncertain significance | Cardiovascular phenotype | 2022-05-09 | criteria provided, single submitter | clinical testing | The p.N824Y variant (also known as c.2470A>T), located in coding exon 16 of the FLNC gene, results from an A to T substitution at nucleotide position 2470. The asparagine at codon 824 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |