Submissions for variant NM_020442.6(VARS2):c.1850C>T (p.Thr617Met)

gnomAD frequency: 0.00008  dbSNP: rs367837827

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413756	SCV000492320	uncertain significance	not specified	2016-12-15	criteria provided, single submitter	clinical testing	The T647M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T647M variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The T647M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Mayo Clinic Laboratories, Mayo Clinic	RCV000676492	SCV000802275	uncertain significance	not provided	2017-06-14	no assertion criteria provided	clinical testing
GenomeConnect, ClinGen	RCV000709983	SCV000840349	not provided	Combined oxidative phosphorylation defect type 20		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.