ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.13207G>A (p.Ala4403Thr)

gnomAD frequency: 0.00003  dbSNP: rs1051206491
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000655556 SCV000777487 uncertain significance RYR1-related disorder 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 4403 of the RYR1 protein (p.Ala4403Thr). 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: 544420). 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.
CeGaT Center for Human Genetics Tuebingen RCV000996906 SCV001151897 uncertain significance not provided 2022-08-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002493065 SCV002781406 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 2021-07-09 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000996906 SCV003814465 uncertain significance not provided 2023-02-03 criteria provided, single submitter clinical testing

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