Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_006757.4(TNNT3):c.636T>C(p.Ile212Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,613,608 control chromosomes in the GnomAD database, including 675 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
TNNT3 (HGNC:11950): (troponin T3, fast skeletal type) The binding of Ca(2+) to the trimeric troponin complex initiates the process of muscle contraction. Increased Ca(2+) concentrations produce a conformational change in the troponin complex that is transmitted to tropomyosin dimers situated along actin filaments. The altered conformation permits increased interaction between a myosin head and an actin filament which, ultimately, produces a muscle contraction. The troponin complex has protein subunits C, I, and T. Subunit C binds Ca(2+) and subunit I binds to actin and inhibits actin-myosin interaction. Subunit T binds the troponin complex to the tropomyosin complex and is also required for Ca(2+)-mediated activation of actomyosin ATPase activity. There are 3 different troponin T genes that encode tissue-specific isoforms of subunit T for fast skeletal-, slow skeletal-, and cardiac-muscle. This gene encodes fast skeletal troponin T protein; also known as troponin T type 3. Alternative splicing results in multiple transcript variants encoding additional distinct troponin T type 3 isoforms. A developmentally regulated switch between fetal/neonatal and adult troponin T type 3 isoforms occurs. Additional splice variants have been described but their biological validity has not been established. Mutations in this gene may cause distal arthrogryposis multiplex congenita type 2B (DA2B). [provided by RefSeq, Oct 2009]
TNNT3 Gene-Disease associations (from GenCC):
distal arthrogryposis type 2B1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
congenital myopathy
Inheritance: AR Classification: STRONG Submitted by: G2P
arthrogryposis, distal, type 2B2
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
nemaline myopathy
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen
digitotalar dysmorphism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Sheldon-hall syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Our verdict: Benign. The variant received -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
Variant 11-1934874-T-C is Benign according to our data. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1934874-T-C is described in CliVar as Benign/Likely_benign. Clinvar id is 31871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.99 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.
Genetic Services Laboratory, University of Chicago
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
-
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Distal arthrogryposis type 2B1Benign:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -