Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000542255 | SCV000650926 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2024-01-22 | criteria provided, single submitter | clinical testing | This variant, c.1935_1937del, results in the deletion of 1 amino acid(s) of the FLNC protein (p.Asp646del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs765300084, gnomAD 0.008%). This variant has been observed in individual(s) with left ventricular non-compaction (PMID: 30471092). ClinVar contains an entry for this variant (Variation ID: 471992). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 | RCV002413600 | SCV002717527 | uncertain significance | Cardiovascular phenotype | 2022-09-28 | criteria provided, single submitter | clinical testing | The c.1935_1937delCGA variant (also known as p.D646del) is located in coding exon 12 of the FLNC gene. This variant results from an in-frame CGA deletion at nucleotide positions 1935 to 1937. This results in the in-frame deletion of an aspartic acid at codon 646. This variant (referred to as c.1933_1935del, p.645del) was detected in a left ventricular non-compaction cohort; however, details were limited (Richard P et al. Clin. Genet., 2019 03;95:356-367). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002491077 | SCV002782929 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26 | 2021-10-20 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV003144348 | SCV003833124 | uncertain significance | not provided | 2021-04-07 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003144348 | SCV004167641 | uncertain significance | not provided | 2023-10-10 | criteria provided, single submitter | clinical testing | Reported as c.1933_1935del using alternate nomenclature in patients with left ventricular non-compaction (LVNC) in the published literature (Richard et al., 2019; Cambon-Viala et al., 2021); at least one patient harbored an additional cardiogenetic variant; In-frame deletion of one amino acid in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30471092, 34088380) |