TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27265	82018;82019;82020	chr2:178564339;178564338;178564337	chr2:179429066;179429065;179429064
N2AB	25624	77095;77096;77097	chr2:178564339;178564338;178564337	chr2:179429066;179429065;179429064
N2A	24697	74314;74315;74316	chr2:178564339;178564338;178564337	chr2:179429066;179429065;179429064
N2B	18200	54823;54824;54825	chr2:178564339;178564338;178564337	chr2:179429066;179429065;179429064
Novex-1	18325	55198;55199;55200	chr2:178564339;178564338;178564337	chr2:179429066;179429065;179429064
Novex-2	18392	55399;55400;55401	chr2:178564339;178564338;178564337	chr2:179429066;179429065;179429064
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-86
• Domain position: 96
• Structural Position: 129
• Q(SASA): 0.3595
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
T/I	rs371129005	0.215	0.125	N	0.37	0.234	None	gnomAD-2.1.1	3.22E-05	None	None	None	None	N	None	3.30715E-04	0	None	0	0	None	0	None	0	7.83E-06	0
T/I	rs371129005	0.215	0.125	N	0.37	0.234	None	gnomAD-3.1.2	1.05195E-04	None	None	None	None	N	None	3.86156E-04	0	0	0	0	None	0	0	0	0	0
T/I	rs371129005	0.215	0.125	N	0.37	0.234	None	gnomAD-4.0.0	1.54936E-05	None	None	None	None	N	None	3.07076E-04	0	None	0	2.23075E-05	None	0	0	8.47637E-07	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
T/A	0.188	likely_benign	0.1729	benign	-0.941	Destabilizing	0.952	D	0.512	neutral	N	0.487512754	None	None	N
T/C	0.6562	likely_pathogenic	0.6426	pathogenic	-0.652	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
T/D	0.8432	likely_pathogenic	0.7754	pathogenic	-0.567	Destabilizing	0.998	D	0.736	deleterious	None	None	None	None	N
T/E	0.6897	likely_pathogenic	0.5884	pathogenic	-0.516	Destabilizing	0.998	D	0.725	deleterious	None	None	None	None	N
T/F	0.4634	ambiguous	0.3877	ambiguous	-0.761	Destabilizing	0.989	D	0.802	deleterious	None	None	None	None	N
T/G	0.7271	likely_pathogenic	0.6855	pathogenic	-1.259	Destabilizing	0.998	D	0.555	neutral	None	None	None	None	N
T/H	0.6137	likely_pathogenic	0.5349	ambiguous	-1.468	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
T/I	0.1999	likely_benign	0.1598	benign	-0.164	Destabilizing	0.125	N	0.37	neutral	N	0.488649832	None	None	N
T/K	0.5232	ambiguous	0.41	ambiguous	-0.89	Destabilizing	0.995	D	0.735	deleterious	None	None	None	None	N
T/L	0.1429	likely_benign	0.1288	benign	-0.164	Destabilizing	0.929	D	0.551	neutral	None	None	None	None	N
T/M	0.12	likely_benign	0.1098	benign	0.042	Stabilizing	0.997	D	0.778	deleterious	None	None	None	None	N
T/N	0.457	ambiguous	0.3903	ambiguous	-0.965	Destabilizing	0.998	D	0.728	deleterious	N	0.515024758	None	None	N
T/P	0.4018	ambiguous	0.3606	ambiguous	-0.389	Destabilizing	0.998	D	0.768	deleterious	N	0.488019733	None	None	N
T/Q	0.5233	ambiguous	0.4543	ambiguous	-1.044	Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
T/R	0.475	ambiguous	0.3667	ambiguous	-0.719	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
T/S	0.3255	likely_benign	0.2938	benign	-1.243	Destabilizing	0.976	D	0.521	neutral	N	0.514517779	None	None	N
T/V	0.1519	likely_benign	0.1309	benign	-0.389	Destabilizing	0.843	D	0.525	neutral	None	None	None	None	N
T/W	0.8191	likely_pathogenic	0.7605	pathogenic	-0.718	Destabilizing	1.0	D	0.739	deleterious	None	None	None	None	N
T/Y	0.5814	likely_pathogenic	0.4978	ambiguous	-0.487	Destabilizing	0.998	D	0.82	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.