Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000320796 | SCV000344748 | uncertain significance | not provided | 2016-08-15 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000798015 | SCV000937607 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2023-11-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1526 of the FLNC protein (p.Arg1526Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 290237). 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. 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. |
Phosphorus, |
RCV001823722 | SCV002073456 | uncertain significance | not specified | 2022-01-18 | criteria provided, single submitter | clinical testing | This missense variant results in an amino acid substitution of Arginine with Cysteine at codon 1526 of the FLNC gene (transcript: NM_001458.4). This variant has an entry in ClinVar (290237) NM_001458.5(FLNC):c.4576C>T (p.Arg1526Cys). This variant occurred in gnomAD with a total MAF of 0 0.0022% and with the highest MAF of 0.0070% in the South Asian population. This position is conserved. In silico functional algorithms predict this variant to be benign (PolyPhen) and tolerated (SIFT). However, no functional studies were performed to confirm either of those predictions. The variant has not occurred in the literature in association with the disease. Considering that this is a rare variant and the available evidence is not enough to ascertain its role in disease, it has been classified as Variant of Uncertain Significance. |
Revvity Omics, |
RCV000320796 | SCV003833177 | uncertain significance | not provided | 2019-10-27 | criteria provided, single submitter | clinical testing |