chr1-201076970-G-A
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP3BP6
The NM_000069.3(CACNA1S):c.1777C>T(p.Arg593Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000774 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R593Q) has been classified as Likely benign.
Frequency
Consequence
NM_000069.3 missense
Scores
Clinical Significance
Conservation
Publications
- congenital myopathy 18Inheritance: AD, AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- hypokalemic periodic paralysis, type 1Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
- malignant hyperthermia, susceptibility to, 5Inheritance: AD Classification: STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
- congenital myopathyInheritance: SD, AR, AD Classification: STRONG Submitted by: Illumina, Genomics England PanelApp
- hypokalemic periodic paralysisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000437 AC: 11AN: 251494 AF XY: 0.0000221 show subpopulations
GnomAD4 exome AF: 0.0000821 AC: 120AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000743 AC XY: 54AN XY: 727248 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74348 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Malignant hyperthermia, susceptibility to, 5;C2749982:Thyrotoxic periodic paralysis, susceptibility to, 1;C3714580:Hypokalemic periodic paralysis, type 1 Uncertain:1
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Hypokalemic periodic paralysis, type 1 Uncertain:1
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not provided Uncertain:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Malignant hyperthermia, susceptibility to, 5;C3714580:Hypokalemic periodic paralysis, type 1 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at