Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000704433 | SCV000833382 | likely pathogenic | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-10-14 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 9 (c.1548_1549+2del) of the FLNC gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FLNC are known to be pathogenic (PMID: 27908349). This variant is present in population databases (rs763330423, gnomAD 0.0009%). 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: 580786). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Ambry Genetics | RCV003165906 | SCV003859335 | uncertain significance | Cardiovascular phenotype | 2023-01-31 | criteria provided, single submitter | clinical testing | The c.1548_1549+2delAAGT variant results from an in-frame deletion of 4 nucleotides between positions c.1548 and c.1549+2 and involves the canonical splice donor site after coding exon 9 of the FLNC gene. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNAdecay; however, direct evidence is unavailable. The exact functional effect of the altered amino acid sequence is unknown. This nucleotide region is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |