chr19-55137179-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_003283.6(TNNT1):c.535C>T(p.Arg179Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000587 in 1,584,526 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R179Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_003283.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNNT1 | NM_003283.6 | c.535C>T | p.Arg179Trp | missense_variant | 11/14 | ENST00000588981.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNT1 | ENST00000588981.6 | c.535C>T | p.Arg179Trp | missense_variant | 11/14 | 1 | NM_003283.6 |
Frequencies
GnomAD3 genomes AF: 0.0000134 AC: 2AN: 148876Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251066Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135774
GnomAD4 exome AF: 0.0000634 AC: 91AN: 1435650Hom.: 0 Cov.: 33 AF XY: 0.0000588 AC XY: 42AN XY: 713888
GnomAD4 genome AF: 0.0000134 AC: 2AN: 148876Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 72480
ClinVar
Submissions by phenotype
Nemaline myopathy 5 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 18, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 465996). This variant has not been reported in the literature in individuals affected with TNNT1-related conditions. This variant is present in population databases (rs757227738, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 179 of the TNNT1 protein (p.Arg179Trp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at