ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.1935_1937del (p.Asp646del)

dbSNP: rs765300084
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Total submissions: 5
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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, 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, Revvity RCV003144348 SCV003833124 uncertain significance not provided 2021-04-07 criteria provided, single submitter clinical testing
GeneDx 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)

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