Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001926648 | SCV002200117 | uncertain significance | X-linked myopathy with postural muscle atrophy | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 261 of the FHL1 protein (p.Asn261Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FHL1-related conditions. 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: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Ambry Genetics | RCV004616881 | SCV005115885 | uncertain significance | Cardiovascular phenotype | 2024-03-24 | criteria provided, single submitter | clinical testing | The p.N261S variant (also known as c.782A>G), located in coding exon 5 of the FHL1 gene, results from an A to G substitution at nucleotide position 782. The asparagine at codon 261 is replaced by serine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |