Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000649154 | SCV000770979 | likely benign | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2024-01-19 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002406443 | SCV002713173 | uncertain significance | Cardiovascular phenotype | 2022-10-17 | criteria provided, single submitter | clinical testing | The p.V601A variant (also known as c.1802T>C), located in coding exon 11 of the FLNC gene, results from a T to C substitution at nucleotide position 1802. The valine at codon 601 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. 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, |
RCV000786311 | SCV004563641 | uncertain significance | not provided | 2023-04-24 | criteria provided, single submitter | clinical testing | The FLNC c.1802T>C; p.Val601Ala variant (rs763590899), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 539420). This variant is found in the general population with an overall allele frequency of 0.0038% (9/239,908 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is deleterious (REVEL: 0.727). Due to limited information, the clinical significance of this variant is uncertain at this time. |
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000786311 | SCV000925079 | uncertain significance | not provided | 2017-09-28 | no assertion criteria provided | provider interpretation | Found in a 14 yo female with incomplete RBBB on EKG and a history of two syncopal episodes during exercise. Her echocardiogram and cardiac MRI were read as normal, and she has no known skeletal myopathy. p.Val601Ala (c.1802T>C) in the FLNC gene (NM_001458.4) Chromosome location 7:128481013 T / C Based on the information reviewed below, we classify this as a VUS, probably benign, concluding that there is not sufficient evidence for its pathogenicity to warrant using it for predictive genetic testing. This variant has not previously been reported in the literature in association with disease, according to the Invitae report. It is present, however, in population databases and is most common in individuals with Latino ancestry like our patient. This is a conservative amino acid change, resulting in the replacement of a nonpolar Valine with a nonpolar Alanine. Valine at this location is well conserved across ~100 vertebrate species for which we have data as are surrounding residues, which may support the functional importance of this region of the protein. There are no Likely Pathogenic or Pathogenic missense variants listed in ClinVar within 10 amino acids to either side. According to the Invitae report, algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant was reported in 9 individuals in the gnomAD database, which includes variant calls on ~140,000 individuals of European, African, Latino, South Asian, Ashkenazi, and East Asian descent. Specifically, the variant was observed in 7 out of 14,839 Latino individuals (for the highest allele frequency: 0.02%), and 2 non-Finnish Europeans. Our patient has Latino ancestry. The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease. The curators made an effort to exclude individuals with severe pediatric diseases. |