rs1319954878
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_000368.5(TSC1):āc.2755A>Gā(p.Lys919Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K919Q) has been classified as Likely benign.
Frequency
Consequence
NM_000368.5 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 |
---|---|---|---|---|---|---|---|
TSC1 | NM_000368.5 | c.2755A>G | p.Lys919Glu | missense_variant | 21/23 | ENST00000298552.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSC1 | ENST00000298552.9 | c.2755A>G | p.Lys919Glu | missense_variant | 21/23 | 1 | NM_000368.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461892Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 727248
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Tuberous sclerosis 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 02, 2023 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt TSC1 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. ClinVar contains an entry for this variant (Variation ID: 574799). This variant has not been reported in the literature in individuals affected with TSC1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 919 of the TSC1 protein (p.Lys919Glu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at