Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV001262961 | SCV001441020 | uncertain significance | Hypertrophic cardiomyopathy 26 | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV001706726 | SCV001934392 | uncertain significance | Distal myopathy with posterior leg and anterior hand involvement | 2020-09-04 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001880049 | SCV002203089 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2022-08-23 | criteria provided, single submitter | clinical testing | 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 983106). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is present in population databases (rs146715204, gnomAD 0.007%). This sequence change falls in intron 18 of the FLNC gene. It does not directly change the encoded amino acid sequence of the FLNC protein. It affects a nucleotide within the consensus splice site. |
Ambry Genetics | RCV002436983 | SCV002749249 | uncertain significance | Cardiovascular phenotype | 2019-04-03 | criteria provided, single submitter | clinical testing | The c.2811+4C>T intronic variant results from a C to T substitution 4 nucleotides after coding exon 18 in the FLNC gene. This nucleotide position is poorly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor/donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |