Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001206223 | SCV001377520 | uncertain significance | X-linked myopathy with postural muscle atrophy | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with serine at codon 274 of the FHL1 protein (p.Pro274Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 | RCV002429880 | SCV002681242 | uncertain significance | Cardiovascular phenotype | 2022-09-12 | criteria provided, single submitter | clinical testing | The p.P274S variant (also known as c.820C>T), located in coding exon 5 of the FHL1 gene, results from a C to T substitution at nucleotide position 820. The proline at codon 274 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |