TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16737	50434;50435;50436	chr2:178612316;178612315;178612314	chr2:179477043;179477042;179477041
N2AB	15096	45511;45512;45513	chr2:178612316;178612315;178612314	chr2:179477043;179477042;179477041
N2A	14169	42730;42731;42732	chr2:178612316;178612315;178612314	chr2:179477043;179477042;179477041
N2B	7672	23239;23240;23241	chr2:178612316;178612315;178612314	chr2:179477043;179477042;179477041
Novex-1	7797	23614;23615;23616	chr2:178612316;178612315;178612314	chr2:179477043;179477042;179477041
Novex-2	7864	23815;23816;23817	chr2:178612316;178612315;178612314	chr2:179477043;179477042;179477041
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-9
• Domain position: 87
• Structural Position: 121
• Q(SASA): 0.1204
• 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/A	None	None	0.005	N	0.365	0.111	0.110078149338	gnomAD-4.0.0	1.59394E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86246E-06	0	0
T/I	None	None	0.012	N	0.515	0.106	0.234412748748	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93751E-06	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	0.086	likely_benign	0.0803	benign	-1.034	Destabilizing	0.005	N	0.365	neutral	N	0.472459067	None	None	N
T/C	0.0722	likely_benign	0.0513	benign	-0.704	Destabilizing	None	N	0.452	neutral	None	None	None	None	N
T/D	0.712	likely_pathogenic	0.6806	pathogenic	-1.012	Destabilizing	0.325	N	0.588	neutral	None	None	None	None	N
T/E	0.6095	likely_pathogenic	0.6075	pathogenic	-0.854	Destabilizing	0.325	N	0.588	neutral	None	None	None	None	N
T/F	0.4316	ambiguous	0.3813	ambiguous	-0.582	Destabilizing	0.356	N	0.571	neutral	None	None	None	None	N
T/G	0.2777	likely_benign	0.2029	benign	-1.434	Destabilizing	0.072	N	0.569	neutral	None	None	None	None	N
T/H	0.4165	ambiguous	0.3828	ambiguous	-1.519	Destabilizing	0.864	D	0.541	neutral	None	None	None	None	N
T/I	0.2203	likely_benign	0.2355	benign	-0.002	Destabilizing	0.012	N	0.515	neutral	N	0.475419558	None	None	N
T/K	0.554	ambiguous	0.5716	pathogenic	-0.695	Destabilizing	0.136	N	0.585	neutral	None	None	None	None	N
T/L	0.1607	likely_benign	0.1534	benign	-0.002	Destabilizing	0.016	N	0.505	neutral	None	None	None	None	N
T/M	0.1483	likely_benign	0.1487	benign	-0.042	Destabilizing	0.356	N	0.554	neutral	None	None	None	None	N
T/N	0.2478	likely_benign	0.2364	benign	-1.134	Destabilizing	0.295	N	0.543	neutral	N	0.474539484	None	None	N
T/P	0.7855	likely_pathogenic	0.7856	pathogenic	-0.314	Destabilizing	0.56	D	0.605	neutral	N	0.47534588	None	None	N
T/Q	0.4012	ambiguous	0.392	ambiguous	-0.983	Destabilizing	0.628	D	0.569	neutral	None	None	None	None	N
T/R	0.4047	ambiguous	0.3976	ambiguous	-0.788	Destabilizing	0.628	D	0.593	neutral	None	None	None	None	N
T/S	0.1413	likely_benign	0.1226	benign	-1.395	Destabilizing	0.024	N	0.415	neutral	N	0.342426132	None	None	N
T/V	0.1282	likely_benign	0.1343	benign	-0.314	Destabilizing	None	N	0.235	neutral	None	None	None	None	N
T/W	0.7655	likely_pathogenic	0.7473	pathogenic	-0.677	Destabilizing	0.864	D	0.566	neutral	None	None	None	None	N
T/Y	0.4353	ambiguous	0.4	ambiguous	-0.349	Destabilizing	0.628	D	0.551	neutral	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.