ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.985G>A (p.Asp329Asn)

dbSNP: rs1966919745
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001931298 SCV002205871 uncertain significance RYR1-related disorder 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 329 of the RYR1 protein (p.Asp329Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. 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 RCV002484620 SCV002781619 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 2021-10-15 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004010924 SCV004821738 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-02-24 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 329 of the RYR1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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