TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30737	92434;92435;92436	chr2:178549417;178549416;178549415	chr2:179414144;179414143;179414142
N2AB	29096	87511;87512;87513	chr2:178549417;178549416;178549415	chr2:179414144;179414143;179414142
N2A	28169	84730;84731;84732	chr2:178549417;178549416;178549415	chr2:179414144;179414143;179414142
N2B	21672	65239;65240;65241	chr2:178549417;178549416;178549415	chr2:179414144;179414143;179414142
Novex-1	21797	65614;65615;65616	chr2:178549417;178549416;178549415	chr2:179414144;179414143;179414142
Novex-2	21864	65815;65816;65817	chr2:178549417;178549416;178549415	chr2:179414144;179414143;179414142
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: Fn3-112
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.2546
• 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/N	None	None	1.0	N	0.651	0.433	0.509228182784	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.2583	likely_benign	0.3023	benign	-0.96	Destabilizing	0.999	D	0.575	neutral	N	0.491425277	None	None	N
T/C	0.6308	likely_pathogenic	0.6864	pathogenic	-1.002	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
T/D	0.9098	likely_pathogenic	0.9368	pathogenic	-1.554	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
T/E	0.8651	likely_pathogenic	0.8908	pathogenic	-1.452	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
T/F	0.4667	ambiguous	0.587	pathogenic	-0.827	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
T/G	0.7151	likely_pathogenic	0.7772	pathogenic	-1.288	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
T/H	0.6541	likely_pathogenic	0.7454	pathogenic	-1.546	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
T/I	0.2117	likely_benign	0.2398	benign	-0.147	Destabilizing	1.0	D	0.731	prob.delet.	N	0.479170372	None	None	N
T/K	0.8281	likely_pathogenic	0.8607	pathogenic	-0.843	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
T/L	0.168	likely_benign	0.2019	benign	-0.147	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
T/M	0.1234	likely_benign	0.1493	benign	-0.056	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
T/N	0.4124	ambiguous	0.4999	ambiguous	-1.246	Destabilizing	1.0	D	0.651	neutral	N	0.484930817	None	None	N
T/P	0.856	likely_pathogenic	0.8825	pathogenic	-0.386	Destabilizing	1.0	D	0.745	deleterious	D	0.53350959	None	None	N
T/Q	0.6884	likely_pathogenic	0.7335	pathogenic	-1.299	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
T/R	0.7722	likely_pathogenic	0.8209	pathogenic	-0.766	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
T/S	0.2755	likely_benign	0.3327	benign	-1.386	Destabilizing	0.999	D	0.534	neutral	N	0.475736878	None	None	N
T/V	0.1767	likely_benign	0.2016	benign	-0.386	Destabilizing	0.999	D	0.552	neutral	None	None	None	None	N
T/W	0.8277	likely_pathogenic	0.8953	pathogenic	-0.894	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
T/Y	0.5549	ambiguous	0.6581	pathogenic	-0.558	Destabilizing	1.0	D	0.813	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.