Submissions for variant NM_004586.3(RPS6KA3):c.212T>G (p.Leu71Ter)

dbSNP: rs2068650679

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001251296	SCV001426837	likely pathogenic	Coffin-Lowry syndrome	2020-07-31	criteria provided, single submitter	clinical testing	Variant summary: RPS6KA3 c.212T>G (p.Leu71X) 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 was absent in 183190 control chromosomes. To our knowledge, no occurrence of c.212T>G in individuals affected with Coffin-Lowry Syndrome 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.
Genetic Services Laboratory, University of Chicago	RCV001819956	SCV002069310	pathogenic	not provided	2018-12-26	criteria provided, single submitter	clinical testing	DNA sequence analysis of the RPS6KA3 gene demonstrated a sequence change in exon 3, c.212T>G, which results in the creation of a premature stop codon at amino acid position 71, p.Leu71*. This pathogenic sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated RPS6KA3 protein with potentially abnormal function. This sequence change is located in a protein domain where other truncating mutations have been previously reported in patients with Coffin-Lowry syndrome. This sequence change has not been observed in population databases (ExAc, gnomAD).