Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001071542 | SCV001236850 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-12-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1982 of the FLNC protein (p.Arg1982His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 864369). 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 | RCV004031152 | SCV003948864 | uncertain significance | Cardiovascular phenotype | 2023-05-17 | criteria provided, single submitter | clinical testing | The c.5945G>A (p.R1982H) alteration is located in exon 36 (coding exon 36) of the FLNC gene. This alteration results from a G to A substitution at nucleotide position 5945, causing the arginine (R) at amino acid position 1982 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Ce |
RCV003425915 | SCV004161045 | uncertain significance | not provided | 2023-08-01 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003973043 | SCV004795488 | uncertain significance | FLNC-related disorder | 2023-12-20 | criteria provided, single submitter | clinical testing | The FLNC c.5945G>A variant is predicted to result in the amino acid substitution p.Arg1982His. This variant was reported in an individual with hypertrophic cardiomyopathy (Table S1, Chumakova et al. 2023. PubMed ID: 38002985). This variant is reported in 0.0016% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |