Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001918844 | SCV002184869 | uncertain significance | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2021-04-28 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FLNC-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces isoleucine with threonine at codon 1554 of the FLNC protein (p.Ile1554Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. |
Ambry Genetics | RCV002334874 | SCV002638094 | uncertain significance | Cardiovascular phenotype | 2021-11-14 | criteria provided, single submitter | clinical testing | The p.I1554T variant (also known as c.4661T>C), located in coding exon 27 of the FLNC gene, results from a T to C substitution at nucleotide position 4661. The isoleucine at codon 1554 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |