rs199473132
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001099404.2(SCN5A):c.1802T>C(p.Val601Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000697 in 1,435,748 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V601L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001099404.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN5A | NM_001099404.2 | c.1802T>C | p.Val601Ala | missense_variant | 12/28 | ENST00000413689.6 | |
SCN5A | NM_000335.5 | c.1802T>C | p.Val601Ala | missense_variant | 12/28 | ENST00000423572.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN5A | ENST00000413689.6 | c.1802T>C | p.Val601Ala | missense_variant | 12/28 | 5 | NM_001099404.2 | P4 | |
SCN5A | ENST00000423572.7 | c.1802T>C | p.Val601Ala | missense_variant | 12/28 | 1 | NM_000335.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.97e-7 AC: 1AN: 1435748Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1AN XY: 709826
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2021 | This sequence change replaces valine with alanine at codon 601 of the SCN5A protein (p.Val601Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 67690). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
not provided, no classification provided | literature only | Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust | - | This variant has been reported in the following publications (PMID:19841300;PMID:20129283). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at