Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001240614 | SCV001413579 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2022-07-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 54 of the FLNC protein (p.Gly54Asp). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with limb-girdle muscle weakness (PMID: 29970176). ClinVar contains an entry for this variant (Variation ID: 966028). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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 | RCV002393619 | SCV002703224 | uncertain significance | Cardiovascular phenotype | 2019-06-21 | criteria provided, single submitter | clinical testing | The p.G54D variant (also known as c.161G>A), located in coding exon 1 of the FLNC gene, results from a G to A substitution at nucleotide position 161. The glycine at codon 54 is replaced by aspartic acid, an amino acid with similar properties. This variant has been detected in conjunction with variants in other genes in an individual with limb-girdle muscle weakness (Fichna JP et al. Hum. Genomics, 2018 07;12:34). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |