Submissions for variant NM_016589.4(TIMMDC1):c.1A>G (p.Met1Val)

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	RCV002308566	SCV002600449	likely pathogenic	Mitochondrial complex 1 deficiency, nuclear type 31	2022-10-11	criteria provided, single submitter	clinical testing	Variant summary: C3orf1 c.1A>G (p.Met1Val) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon (Met207). The variant allele was found at a frequency of 8e-06 in 251292 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1A>G in individuals affected with Mitochondrial Complex 1 Deficiency, Nuclear Type 31 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. At least one truncation variant (p.Arg129Ter) has been reported between p.Met1 and p.Met207 in ClinVar database, suggesting p.Met207 is unlikely to be utilized as alternative start codon and maintain protein function. Based on the evidence outlined above, the variant was classified as likely pathogenic.