Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000403247 | SCV000341973 | uncertain significance | not provided | 2016-06-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001041037 | SCV001204631 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2022-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1378 of the FLNC protein (p.Ala1378Val). This variant is present in population databases (rs748008658, gnomAD 0.005%). 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: 287999). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FLNC protein function. 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 | RCV002328785 | SCV002627187 | uncertain significance | Cardiovascular phenotype | 2021-06-08 | criteria provided, single submitter | clinical testing | The p.A1378V variant (also known as c.4133C>T), located in coding exon 24 of the FLNC gene, results from a C to T substitution at nucleotide position 4133. The alanine at codon 1378 is replaced by valine, 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. |
Prevention |
RCV003401261 | SCV004111202 | uncertain significance | FLNC-related disorder | 2022-12-29 | criteria provided, single submitter | clinical testing | The FLNC c.4133C>T variant is predicted to result in the amino acid substitution p.Ala1378Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0047% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-128486804-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |