rs931949929
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM5BS2
The NM_001037.5(SCN1B):āc.316A>Gā(p.Ile106Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000185 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I106F) has been classified as Pathogenic.
Frequency
Consequence
NM_001037.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN1B | NM_001037.5 | c.316A>G | p.Ile106Val | missense_variant | 3/6 | ENST00000262631.11 | |
SCN1B | NM_199037.5 | c.316A>G | p.Ile106Val | missense_variant | 3/3 | ||
SCN1B | NM_001321605.2 | c.217A>G | p.Ile73Val | missense_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN1B | ENST00000262631.11 | c.316A>G | p.Ile106Val | missense_variant | 3/6 | 1 | NM_001037.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461892Hom.: 0 Cov.: 33 AF XY: 0.0000220 AC XY: 16AN XY: 727246
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Brugada syndrome 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 23, 2023 | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 106 of the SCN1B protein (p.Ile106Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1706108). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 | Mar 14, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2023 | The p.I106V variant (also known as c.316A>G), located in coding exon 3 of the SCN1B gene, results from an A to G substitution at nucleotide position 316. The isoleucine at codon 106 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at