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Variant: NM_000540.3(RYR1):c.1597C>A (p.Arg533Ser)

CA10607101

291315 (ClinVar)

Gene: RYR1
Condition: malignant hyperthermia, susceptibility to, 1
Inheritance Mode: Autosomal dominant inheritance
UUID: ef32acc4-b195-48ee-9f7e-289e729417a0
Approved on: 2023-04-07
Published on: 2023-04-07

HGVS expressions

NM_000540.3:c.1597C>A
NM_000540.3(RYR1):c.1597C>A (p.Arg533Ser)
NC_000019.10:g.38455471C>A
CM000681.2:g.38455471C>A
NC_000019.9:g.38946111C>A
CM000681.1:g.38946111C>A
NC_000019.8:g.43637951C>A
NG_008866.1:g.26772C>A
ENST00000599547.6:n.1597C>A
ENST00000359596.8:c.1597C>A
ENST00000355481.8:c.1597C>A
ENST00000359596.7:n.1597C>A
ENST00000360985.7:c.1597C>A
NM_000540.2:c.1597C>A
NM_001042723.1:c.1597C>A
NM_001042723.2:c.1597C>A
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Uncertain Significance

Met criteria codes 2
PP3_Moderate PM1
Not Met criteria codes 2
BS1 BA1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Malignant Hyperthermia Susceptibility VCEP
This pathogenicity assessment is relevant only for malignant hyperthermia susceptibility (MHS) inherited in an autosomal dominant pattern. Variants in RYR1 can also cause other myopathies inherited in an autosomal dominant pattern or in an autosomal recessive pattern. Some of these disorders may predispose individuals to malignant hyperthermia. RYR1 variants may also contribute to a malignant hyperthermia reaction in combination with other genetic and non-genetic factors and the clinician needs to consider such factors in making management decisions. This sequence variant predicts a substitution of Arginine with Serine at codon 533 of the RYR1 protein, p.(Arg533Ser). This variant is not present in a large population database (gnomAD) at the time this variant was interpreted. No publications were identified that reported this variant in individuals with a personal or family history of MH. The variant is present in ClinVar. No functional studies were identified for this variant. This variant resides in a region of RYR1 considered to be a hotspot for pathogenic variants that contribute to MHS, PM1 (PMID: 21118704). A REVEL score >0.85 (0.86) supports a pathogenic status for this variant, PP3_Moderate. This variant has been classified as a Variant of Unknown Significance. Criteria implemented: PM1, PP3_Moderate.
Met criteria codes
PP3_Moderate
A REVEL score >0.85 (0.86) supports a pathogenic status for this variant, PP3_Moderate.
PM1
This variant resides in a region of RYR1 considered to be a hotspot for pathogenic variants that contribute to MHS, PM1 (PMID: 21118704).
Not Met criteria codes
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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