Description
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 4842 of the RYR1 protein (p.Val4842Met). This variant is present in population databases (rs193922879, gnomAD 0.07%). This missense change has been observed in individual(s) with with autosomal recessive congenital myopathy and an individual affected with malignant hyperthermia susceptibility. In some cases, this variant occurred on the same chromosome as the c.10348–6C>G variant (PMID: 18253926, 20839240, 21062345, 21455645, 23394784, 23553484, 23553787, 26019235, 27854218, 28818389). ClinVar contains an entry for this variant (Variation ID: 133075). 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.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |