Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV004555186 | SCV005044120 | likely pathogenic | Cardiac-urogenital syndrome | 2022-06-14 | criteria provided, single submitter | clinical testing | The de novo c.859_1591-84del, p.(Leu287_Arg530del) variant is a ~5.5KB deletion on the long arm of chromosome 11 (11q12.2). This deletion encompasses the C-terminal part of exon 6, as well as exon 7-11 of the canonical MYRF transcript, as well as intervening and flanking intronic sequences. This is predicted to lead to an in-frame loss of amino acids p.Leu287 through p.Arg530 (loss of 244/1151 amino acids, ~21% of the protein) including a part of the NDT80 DNA-Binding domain (UniProtKB: Q9Y2G1). This variant is absent from gnomAD SVs v2.1 as well as the Database of Genomic Variants (DGV), suggesting it is not a common benign variant in the populations represented in that database. In-frame microdeletions in MYRF gene have not been reported in individuals with MYRF-related disorders, but de novo missense and loss-of-function variants in the DNA binding domain have been reported as pathogenic in individuals with MYRF-related disorders [PMID: 31069960] and functional studies have shown that these variants alter the transcription factor function of MYRF by haploinsufficiency (F387S, Q403H, and L479V) or dominant negative effect (G435R) [PMID: 33798553]. Based on the available evidence, the de novo heterozygous c.859_1591-84del, p.(Leu287_Arg530del) variant identified in the MYRF gene is reported as Likely Pathogenic. |