Submissions for variant NM_198076.6(COX20):c.185dup (p.Val63fs)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002281788	SCV002572187	likely pathogenic	Mitochondrial complex 4 deficiency, nuclear type 11	2022-08-19	criteria provided, single submitter	clinical testing	Variant summary: COX20 c.185dupG (p.Val63SerfsX16) results in a premature termination codon located in the penultimate exon, which is not expected to cause nonsense mediated decay (NMD), but is predicted to cause a truncation of the encoded protein, removing a large part of the 118 amino acid long protein. A truncation downstream of this position has been reported in an affected individual (PMID 33751098), who carried a functionally characterized, (likely) pathogenic missense variant in trans. The variant was absent in 251118 control chromosomes (gnomAD). To our knowledge, no occurrence of c.185dupG in individuals affected with Mitochondrial Complex 4 Deficiency, Nuclear Type 11 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.