Submissions for variant NM_020442.6(VARS2):c.1346G>A (p.Trp449Ter)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Revvity Omics, Revvity	RCV003139263	SCV003820355	uncertain significance	Combined oxidative phosphorylation defect type 20	2021-01-25	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003139263	SCV004039378	pathogenic	Combined oxidative phosphorylation defect type 20	2023-08-24	criteria provided, single submitter	clinical testing	Variant summary: VARS2 c.1346G>A (p.Trp449X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 0.00015 in 250068 control chromosomes (gnomAD), predominantly at a frequency of 0.0012 within the South Asian subpopulation in the gnomAD database. To our knowledge, no occurrence of c.1346G>A in individuals affected with Combined Oxidative Phosphorylation Defect Type 20 and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as pathogenic.
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV004697269	SCV005198978	likely pathogenic	not provided	2022-07-28	criteria provided, single submitter	clinical testing