rs397517955
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP2PP3_Strong
The NM_001099404.2(SCN5A):c.5009T>C(p.Ile1670Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. I1670V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001099404.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN5A | NM_001099404.2 | c.5009T>C | p.Ile1670Thr | missense_variant | 28/28 | ENST00000413689.6 | |
SCN5A | NM_000335.5 | c.5006T>C | p.Ile1669Thr | missense_variant | 28/28 | ENST00000423572.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN5A | ENST00000413689.6 | c.5009T>C | p.Ile1670Thr | missense_variant | 28/28 | 5 | NM_001099404.2 | P4 | |
SCN5A | ENST00000423572.7 | c.5006T>C | p.Ile1669Thr | missense_variant | 28/28 | 1 | NM_000335.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome Cov.: 35
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 03, 2012 | The Ile1670Thr variant in SCN5A has not been reported in the literature nor prev iously identified by our laboratory. The affected amino acid is highly conserved in evolution, suggesting that a change at this position would impact the protei n. Other computational analyses (biochemical amino acid properties, AlignGVGD, P olyPhen2, and SIFT) also support a disease causing role, though this information is not predictive enough to determine pathogenicity. Additional information is needed to fully assess the clinical significance of the Ile1670Thr variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at