ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.12787G>A (p.Glu4263Lys)

dbSNP: rs1471120810
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001068340 SCV001233447 uncertain significance RYR1-related disorder 2022-06-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 4263 of the RYR1 protein (p.Glu4263Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 861754). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RYR1 protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV002489703 SCV002793769 uncertain significance Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome 2021-07-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV004671210 SCV005161784 uncertain significance Inborn genetic diseases 2024-03-25 criteria provided, single submitter clinical testing The c.12787G>A (p.E4263K) alteration is located in exon 91 (coding exon 91) of the RYR1 gene. This alteration results from a G to A substitution at nucleotide position 12787, causing the glutamic acid (E) at amino acid position 4263 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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