Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV000408634 | SCV000484419 | pathogenic | Severe X-linked myotubular myopathy | 2022-09-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with X-linked centronuclear myopathy (MIM#310400). (I) 0109 - This gene is associated with X-linked recessive disease; however, manifesting female carriers of pathogenic variants who present with a range of clinical severity and skewed X-inactivation are increasingly being reported (GeneReviews, PMID: 28685322). (I) 0115 - Variants in this gene are known to have variable expressivity. Female carriers of pathogenic variants have been reported with a range of clinical severity, ranging from severe neonatal and generalised weakness, to milder adult forms (PMID: 28685322). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other null variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. There are at least ten NMD-predicted variants that have been classified as pathogenic or likely pathogenic (DECIPHER). (SP) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated family. This variant has been reported in a male fetus whose brother was clinically diagnosed with X-linked myotubular myopathy and carried the same variant (PMID: 26898940). (SP) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |