ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.13168G>A (p.Glu4390Lys)

dbSNP: rs1413644550
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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 RCV002016522 SCV002298087 uncertain significance RYR1-related disorder 2022-09-01 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 4390 of the RYR1 protein (p.Glu4390Lys). This variant is not present in population databases (gnomAD no frequency). 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: 1509002). 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 RCV002507793 SCV002817043 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 2021-10-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV002545546 SCV003602584 uncertain significance Inborn genetic diseases 2022-02-02 criteria provided, single submitter clinical testing The c.13168G>A (p.E4390K) 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 13168, causing the glutamic acid (E) at amino acid position 4390 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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