rs770079408
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_003283.6(TNNT1):c.566G>T(p.Arg189Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,370,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 7.3e-7 ( 0 hom. )
Consequence
TNNT1
NM_003283.6 missense
NM_003283.6 missense
Scores
14
4
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.22
Genes affected
TNNT1 (HGNC:11948): (troponin T1, slow skeletal type) This gene encodes a protein that is a subunit of troponin, which is a regulatory complex located on the thin filament of the sarcomere. This complex regulates striated muscle contraction in response to fluctuations in intracellular calcium concentration. This complex is composed of three subunits: troponin C, which binds calcium, troponin T, which binds tropomyosin, and troponin I, which is an inhibitory subunit. This protein is the slow skeletal troponin T subunit. Mutations in this gene cause nemaline myopathy type 5, also known as Amish nemaline myopathy, a neuromuscular disorder characterized by muscle weakness and rod-shaped, or nemaline, inclusions in skeletal muscle fibers which affects infants, resulting in death due to respiratory insufficiency, usually in the second year. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.985
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251160Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135796
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GnomAD4 exome AF: 7.30e-7 AC: 1AN: 1370320Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 680618
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33
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GnomAD4 genome
GnomAD4 genome
Cov.:
30
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
.;.;.;D;D;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
.;D;D;D;D;D;.;.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
.;.;M;.;M;.;.;.;.
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
.;D;D;.;.;.;.;.;.
REVEL
Pathogenic
Sift
Pathogenic
.;D;D;.;.;.;.;.;.
Sift4G
Uncertain
D;D;D;D;D;D;D;D;.
Polyphen
D;D;D;.;D;.;.;.;.
Vest4
MutPred
0.86
.;.;Loss of ubiquitination at K190 (P = 0.0364);.;Loss of ubiquitination at K190 (P = 0.0364);.;.;.;Loss of ubiquitination at K190 (P = 0.0364);
MVP
MPC
1.6
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at