Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV000011852 | SCV002769079 | pathogenic | 3-Methylglutaconic aciduria type 2 | 2022-02-02 | 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 Barth syndrome (MIM#302060). (I) 0109 - This gene is associated with X-linked recessive disease. Typically female carriers do not manifest disease due to skewed X-inactivation of the mutant allele. However, affected females have been reported either due to biallelic mutation or monoallelic with skewed X-inactivation of the wild type allele (GeneReviews). (I) 0115 - Variants in this gene are known to have variable expressivity with intrafamilial variability (OMIM). (I) 0202 - 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), but is located in an exon that may undergo alternative splicing. (SP) 0219 - This variant is non-coding in alternative transcripts, but is coding in the ClinVar predominant transcript. (I) 0253 - This variant is hemizygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0807 - This variant has no previous evidence of pathogenicity. It has been previously reported in this same family by Bione, S. et al. (PMID:8630491). (I) 0903 - This variant has limited evidence for segregation with disease. This variant was found in this proband, his unaffected mother and two affected male cousins (PMID: 8630491). (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 |
| OMIM | RCV000011852 | SCV000032085 | pathogenic | 3-Methylglutaconic aciduria type 2 | 1996-04-01 | no assertion criteria provided | literature only |