Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001959413 | SCV002247595 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 684 of the FLNC protein (p.Val684Leu). This variant is present in population databases (rs769221710, gnomAD 0.01%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 30411535). ClinVar contains an entry for this variant (Variation ID: 1466077). 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 | RCV002423157 | SCV002726547 | uncertain significance | Cardiovascular phenotype | 2020-02-21 | criteria provided, single submitter | clinical testing | The p.V684L variant (also known as c.2050G>C), located in coding exon 13 of the FLNC gene, results from a G to C substitution at nucleotide position 2050. The valine at codon 684 is replaced by leucine, an amino acid with highly similar properties. This variant was reported in a hypertrophic cardiomyopathy cohort; however, clinical details were limited (Cui H et al. Mol Genet Genomic Med, 2018 11;6:1104-1113). 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. |
| ARUP Laboratories, |
RCV003738118 | SCV004563580 | uncertain significance | not provided | 2023-11-09 | criteria provided, single submitter | clinical testing | The FLNC c.2050G>C; p.Val684Leu variant (rs769221710) is reported in the literature in one individual affected with hypertrophic cardiomyopathy (Cui 2018). This variant is also reported in ClinVar (Variation ID: 1466077). This variant is only observed on four alleles in the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.547). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Cui H et al. Mutation profile of FLNC gene and its prognostic relevance in patients with hypertrophic cardiomyopathy. Mol Genet Genomic Med. 2018 Nov;6(6):1104-1113. PMID: 30411535. |