Submissions for variant NM_001035.3(RYR2):c.9259C>T (p.Pro3087Ser)

gnomAD frequency: 0.00002  dbSNP: rs777736127

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002568867	SCV003272058	likely benign	Catecholaminergic polymorphic ventricular tachycardia 1	2022-07-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003235582	SCV003934698	uncertain significance	not specified	2023-05-22	criteria provided, single submitter	clinical testing	Variant summary: RYR2 c.9259C>T (p.Pro3087Ser) 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 allele was found at a frequency of 4.3e-06 in 234946 control chromosomes (gnomAD). 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.9259C>T in individuals affected with Catecholaminergic Polymorphic Ventricular Tachycardia and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528412	SCV001740130	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001528412	SCV001929490	uncertain significance	not provided		no assertion criteria provided	clinical testing