rs569880910
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 5P and 5B. PM1PM5PP2BP4BS2
The NM_001165963.4(SCN1A):c.607G>A(p.Val203Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000931 in 1,611,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. V203D) has been classified as Pathogenic.
Frequency
Consequence
NM_001165963.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN1A | NM_001165963.4 | c.607G>A | p.Val203Ile | missense_variant | 8/29 | ENST00000674923.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN1A | ENST00000674923.1 | c.607G>A | p.Val203Ile | missense_variant | 8/29 | NM_001165963.4 | P4 | ||
SCN1A-AS1 | ENST00000651574.1 | n.487+16809C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 151938Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249864Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135076
GnomAD4 exome AF: 0.00000822 AC: 12AN: 1459516Hom.: 0 Cov.: 31 AF XY: 0.00000689 AC XY: 5AN XY: 726120
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152056Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74342
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 24, 2023 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 203 of the SCN1A protein (p.Val203Ile). This variant is present in population databases (rs569880910, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 426348). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN1A protein function. 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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 01, 2018 | The V203I variant in the SCN1A gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The V203I variant is observed in 6/275,664 (0.0022%) global alleles in large population cohorts (Lek et al., 2016). The V203I variant is a conservative amino acid substitution and is predicted to be in the transmembrane segment S3 of the first homologous domain of the SCN1A protein. In silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. A missense variant in a nearby residue (T199R) has been reported in the Human Gene Mutation Database in association with an SCN1A-related disorder (Stenson et al., 2014), suggesting a functional importance for this region of the protein. We interpret V203I as a variant of uncertain significance. - |
Seizure Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Strasbourg University Hospital | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at