Submissions for variant NM_153704.6(TMEM67):c.2522A>C (p.Gln841Pro)

dbSNP: rs863225234

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
UW Hindbrain Malformation Research Program, University of Washington	RCV000201610	SCV000256515	pathogenic	Joubert syndrome 6	2015-02-23	criteria provided, single submitter	research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001804937	SCV002050838	uncertain significance	not specified	2021-12-09	criteria provided, single submitter	clinical testing	Variant summary: TMEM67 c.2522A>C (p.Gln841Pro) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251162 control chromosomes (gnomAD). c.2522A>C has been reported in the literature in individuals affected with Joubert Syndrome And Related Disorders (Doherty_2010 and Suzuki_2016). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.