ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.2780C>T (p.Thr927Met)

gnomAD frequency: 0.00002  dbSNP: rs751728775
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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 RCV001243850 SCV001417035 uncertain significance RYR1-related disorder 2022-08-22 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 927 of the RYR1 protein (p.Thr927Met). This variant is present in population databases (rs751728775, gnomAD 0.01%). 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: 968662). 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 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 RCV002484350 SCV002790384 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 2021-09-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV004034764 SCV004945827 uncertain significance Inborn genetic diseases 2024-01-24 criteria provided, single submitter clinical testing The c.2780C>T (p.T927M) alteration is located in exon 22 (coding exon 22) of the RYR1 gene. This alteration results from a C to T substitution at nucleotide position 2780, causing the threonine (T) at amino acid position 927 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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