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NM_000540.3(RYR1):c.14552T>C (p.Leu4851Pro) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 17, 2017
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000489943.1

Allele description [Variation Report for NM_000540.3(RYR1):c.14552T>C (p.Leu4851Pro)]

NM_000540.3(RYR1):c.14552T>C (p.Leu4851Pro)

Gene:
RYR1:ryanodine receptor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.2
Genomic location:
Preferred name:
NM_000540.3(RYR1):c.14552T>C (p.Leu4851Pro)
HGVS:
  • NC_000019.10:g.38580410T>C
  • NG_008866.1:g.151711T>C
  • NM_000540.3:c.14552T>CMANE SELECT
  • NM_001042723.2:c.14537T>C
  • NP_000531.2:p.Leu4851Pro
  • NP_000531.2:p.Leu4851Pro
  • NP_001036188.1:p.Leu4846Pro
  • LRG_766t1:c.14552T>C
  • LRG_766:g.151711T>C
  • LRG_766p1:p.Leu4851Pro
  • NC_000019.9:g.39071050T>C
  • NM_000540.2:c.14552T>C
Protein change:
L4846P
Links:
dbSNP: rs1085307631
NCBI 1000 Genomes Browser:
rs1085307631
Molecular consequence:
  • NM_000540.3:c.14552T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042723.2:c.14537T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: CN517202

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000576897GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Pathogenic
(Apr 17, 2017) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000576897.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The L4851P variant in the RYR1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The L4851P variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L4851P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (A4846V, V4849I, Y4850C, T4853I, A4856G) have been reported in the Human Gene Mutation Database in association with RYR1-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret L4851P as a pathogenic variant.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 5, 2022