ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.3145G>A (p.Gly1049Ser)

gnomAD frequency: 0.00001  dbSNP: rs990842315
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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 RCV000655510 SCV000777441 uncertain significance RYR1-related disorder 2022-06-04 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1049 of the RYR1 protein (p.Gly1049Ser). 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 missense change has been observed in individual(s) with myopathy (PMID: 22473935, 25960145). ClinVar contains an entry for this variant (Variation ID: 544388). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV002477467 SCV002792758 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 2021-10-19 criteria provided, single submitter clinical testing
GenomeConnect - Invitae Patient Insights Network RCV001535636 SCV001749664 not provided Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 12-08-2017 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.
GenomeConnect, ClinGen RCV000655510 SCV002075176 not provided RYR1-related disorder no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 05-29-2019 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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