ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.13276_13278GAA[2] (p.Glu4428del) (rs869025516)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208370 SCV000264196 uncertain significance Primary familial hypertrophic cardiomyopathy 2015-02-24 criteria provided, single submitter clinical testing
GeneDx RCV000414609 SCV000491843 uncertain significance not provided 2016-11-17 criteria provided, single submitter clinical testing The normal sequence with the bases that are deleted in brackets is: AGAA[delGAA]AAGG. A variant of uncertain significance has been identified in the RYR2 gene. The c.13282_13284delGAA variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 5,900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.13282_13284delGAA variant results in the deletion of a conserved Glutamic acid residue at codon 4428 in the RYR2 gene. However, as this is an in-frame deletion, it is not expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000414609 SCV001147781 uncertain significance not provided 2019-01-01 criteria provided, single submitter clinical testing
Invitae RCV001034728 SCV001198021 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2019-11-26 criteria provided, single submitter clinical testing This variant, c.13282_13284del, results in the deletion of 1 amino acid(s) of the RYR2 protein (p.Glu4428del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs755465177, ExAC 0.004%). This variant has not been reported in the literature in individuals with RYR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 222798). Experimental studies and prediction algorithms are not available or were not evaluated for this variant, and the functional significance of the affected amino acid(s) 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.
Color RCV001192094 SCV001360066 uncertain significance Cardiomyopathy 2019-09-17 criteria provided, single submitter clinical testing

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