rs794728916
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM4PP3
The NM_001099404.2(SCN5A):c.5529_5543del(p.Ser1844_Ile1848del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 33)
Consequence
SCN5A
NM_001099404.2 inframe_deletion
NM_001099404.2 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
SCN5A (HGNC:10593): (sodium voltage-gated channel alpha subunit 5) The protein encoded by this gene is an integral membrane protein and tetrodotoxin-resistant voltage-gated sodium channel subunit. This protein is found primarily in cardiac muscle and is responsible for the initial upstroke of the action potential in an electrocardiogram. Defects in this gene have been associated with long QT syndrome type 3 (LQT3), atrial fibrillation, cardiomyopathy, and Brugada syndrome 1, all autosomal dominant cardiac diseases. Alternative splicing results in several transcript variants encoding different isoforms. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
?
In a region_of_interest Interaction with FGF13 (size 62) in uniprot entity SCN5A_HUMAN there are 10 pathogenic changes around while only 0 benign (100%) in NM_001099404.2
PM4
?
Nonframeshift variant in NON repetitive region in NM_001099404.2.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN5A | NM_000335.5 | c.5526_5540del | p.Ser1843_Ile1847del | inframe_deletion | 28/28 | ENST00000423572.7 | |
SCN5A | NM_001099404.2 | c.5529_5543del | p.Ser1844_Ile1848del | inframe_deletion | 28/28 | ENST00000413689.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN5A | ENST00000413689.6 | c.5529_5543del | p.Ser1844_Ile1848del | inframe_deletion | 28/28 | 5 | NM_001099404.2 | P4 | |
SCN5A | ENST00000423572.7 | c.5526_5540del | p.Ser1843_Ile1847del | inframe_deletion | 28/28 | 1 | NM_000335.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 14, 2016 | In summary, this is a novel in-frame deletion with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SCN5A-related disease. ClinVar contains an entry for this variant (Variation ID: 201563). This sequence change deletes 15 nucleotides from exon 28 of the SCN5A mRNA (c.5529_5543delGAGTGGGGACCGCAT). This leads to the deletion of 5 amino acid residue(s) in the SCN5A protein (p.Ser1844_Ile1848del) but otherwise preserves the integrity of the reading frame. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 20, 2018 | The c.5529_5543del variant in the SCN5A gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. c.5529_5543del results in an in-frame deletion of five amino acids positions 1844-1848 in the SCN5A gene. Other in-frame deletions have been reported in the SCN5A gene in association with arrhythmia. With the clinical and molecular information available at this time, we cannot definitively determine if c.5529_5543del is a disease-causing mutation or a rare benign variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at