Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000814736 | SCV000955158 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2197 of the FLNC protein (p.Arg2197Gln). This variant is present in population databases (rs760535041, gnomAD 0.002%). 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: 658010). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 | RCV002372293 | SCV002667171 | uncertain significance | Cardiovascular phenotype | 2021-09-16 | criteria provided, single submitter | clinical testing | The p.R2197Q variant (also known as c.6590G>A), located in coding exon 40 of the FLNC gene, results from a G to A substitution at nucleotide position 6590. The arginine at codon 2197 is replaced by glutamine, an amino acid with highly 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. |
Prevention |
RCV003918275 | SCV004728517 | uncertain significance | FLNC-related disorder | 2023-12-08 | criteria provided, single submitter | clinical testing | The FLNC c.6590G>A variant is predicted to result in the amino acid substitution p.Arg2197Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 2 of ~247,000 alleles in gnomAD (http://gnomad.broadinstitute.org/variant/7-128494133-G-A?dataset=gnomad_r2_1). An alternate nucleotide change affecting the same amino acid (p.Arg2197Trp) has been reported in individuals with cardiomyopathy (Table S4, Restrepo-Cordoba et al. 2017. PubMed ID: 28138913; Table 1, Al-Hassnan et al. 2020. PubMed ID: 32870709). At this time, the clinical significance of the c.6590G>A (p.Arg2197Gln) variant is uncertain due to the absence of conclusive functional and genetic evidence. |