ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.14421_14423CTT[2] (p.Phe4810del) (rs1555803810)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520157 SCV000617754 uncertain significance not provided 2018-08-07 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the RYR1gene. The c.14427_14429delCTT variant has been reported previously (using alternative nomenclature) in trans with a missense variant in an individual with a RYR1-related myopathy (Bharucha-Goebel et al., 2013) The c.14427_14429delCTT variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.14427_14429delCTT variant results in an in-frame deletion of one amino acid, denoted p.Phe4810del. In silico analysis predicts this variant is probably damaging to the protein structure/function. The deleted amnio acid occurs at a position that is conserved. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000804563 SCV000944479 uncertain significance RYR1-Related Disorders 2018-09-17 criteria provided, single submitter clinical testing This variant, c.14427_14429delCTT, results in the deletion of 1 amino acid of the RYR1 protein (p.Phe4810del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with autosomal recessive central core disease (PMID: 23553484). This variant is also known as p.Phe4808del in the literature. ClinVar contains an entry for this variant (Variation ID: 449523). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid 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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