ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.8573_8578TGGAGT[1] (p.Leu2860_Glu2861del) (rs794728835)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182898 SCV000235287 uncertain significance not provided 2012-02-22 criteria provided, single submitter clinical testing An in-frame deletion of 6 nucleotides was identified in exon 58 of the RYR2 gene. The sequence with the bases that are deleted in braces is: GAGT{TGGAGT}CCAA. This variant is denoted c.8579_8584delTGGAGT at the cDNA level and p.Leu2860_Glu2861del at the protein level. The c.8579_8584delTGGAGT variant in the RYR2 gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. This variant results in the in-frame deletion of two amino acids, Leucine and Glutamic acid. While an in-fame deletion (c.14206_14208delACC) has been reported as a pathogenic mutation in the transmembrane region of RYR2, the c.8579_8584delTGGAGT variant does not occur in any of the RYR2 mutation hot spots (Medeiros-Domingo A et al., 2009). In addition, no mutations in nearby codons have been reported, suggesting this region of the protein may tolerate change. In summary, we cannot determine whether the c.8579_8584delTGGAGT variant is a disease-causing mutation or a benign variant. The variant is found in ARVC panel(s).
Invitae RCV000795347 SCV000934803 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2018-09-10 criteria provided, single submitter clinical testing This variant, c.8579_8584del, results in the deletion of 2 amino acids of the RYR2 protein (p.Leu2860_Glu2861del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with RYR2-related disease. ClinVar contains an entry for this variant (Variation ID: 201408). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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