rs369639550
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BS2
The NM_003280.3(TNNC1):c.337G>A(p.Asp113Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,916 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. D113E) has been classified as Uncertain significance.
Frequency
Consequence
NM_003280.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNNC1 | NM_003280.3 | c.337G>A | p.Asp113Asn | missense_variant | 5/6 | ENST00000232975.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNC1 | ENST00000232975.8 | c.337G>A | p.Asp113Asn | missense_variant | 5/6 | 1 | NM_003280.3 | P1 | |
TNNC1 | ENST00000496590.1 | c.205G>A | p.Asp69Asn | missense_variant | 4/4 | 2 | |||
TNNC1 | ENST00000461086.1 | n.268G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152106Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251146Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135852
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461810Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727212
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152106Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74292
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1Z;C2750472:Hypertrophic cardiomyopathy 13 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 113 of the TNNC1 protein (p.Asp113Asn). This variant is present in population databases (rs369639550, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TNNC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 567523). 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 | Dec 04, 2018 | Reported in one individual with sudden unexplained death; however, no additional clinical or segregation details are available and this individual harbored multiple other cardiogenetic variants (Sanchez et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27930701) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at