Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002470490 | SCV002767999 | uncertain significance | Pyruvate dehydrogenase E1-alpha deficiency | 2021-05-06 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS - 3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with pyruvate dehydrogenase E1-alpha deficiency (MIM# 312170). (I) 0110 - This gene is associated with X-linked dominant disease. (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. (N) 0219 - This variant is non-coding in all other alternative transcripts (UCSC, NCBI). (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v2) <0.001 for a dominant condition (0 heterozygotes, 0 homozygotes, 1 hemizygote). (SP) 0309 - An alternative frameshift variant that creates a premature stop in the same exon (p.(His51Serfs*4)), has been observed in gnomAD (v3) (5 heterozygotes, 0 homozygotes, 7 hemizygotes). (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |