Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003765487 | SCV004570115 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-11-19 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 2160 of the FLNC protein (p.Ile2160Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with restrictive cardiomyopathy (PMID: 26666891). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 253127). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FLNC protein function. Experimental studies have shown that this missense change does not substantially affect FLNC function (PMID: 26666891). 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. |
| OMIM | RCV000239590 | SCV000297925 | pathogenic | Cardiomyopathy, familial restrictive, 5 | 2016-07-21 | no assertion criteria provided | literature only |