Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001975118 | SCV002238407 | pathogenic | X-linked myopathy with postural muscle atrophy | 2023-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 276 of the FHL1 protein (p.Cys276Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Emery-Dreifuss muscular dystrophy (PMID: 19716112). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1459000). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Studies have shown that this missense change does not significantly alter or has an unclear effect on FHL1 gene expression (PMID: 19716112, 22523091, 24634512). This variant disrupts the p.Cys276 amino acid residue in FHL1. Other variant(s) that disrupt this residue have been observed in individuals with FHL1-related conditions (PMID: 22523091; Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |