TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15466	46621;46622;46623	chr2:178620021;178620020;178620019	chr2:179484748;179484747;179484746
N2AB	13825	41698;41699;41700	chr2:178620021;178620020;178620019	chr2:179484748;179484747;179484746
N2A	12898	38917;38918;38919	chr2:178620021;178620020;178620019	chr2:179484748;179484747;179484746
N2B	6401	19426;19427;19428	chr2:178620021;178620020;178620019	chr2:179484748;179484747;179484746
Novex-1	6526	19801;19802;19803	chr2:178620021;178620020;178620019	chr2:179484748;179484747;179484746
Novex-2	6593	20002;20003;20004	chr2:178620021;178620020;178620019	chr2:179484748;179484747;179484746
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-106
• Domain position: 76
• Structural Position: 161
• Q(SASA): 0.7554
• Predicted PPI site: I

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
D/H	rs758950651	0.319	0.999	D	0.732	0.557	0.599286835281	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9E-06	0
D/Y	None	None	1.0	D	0.729	0.711	0.852740806646	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
D/A	0.4534	ambiguous	0.5015	ambiguous	0.033	Stabilizing	0.977	D	0.674	neutral	D	0.548224273	None	None	I
D/C	0.9249	likely_pathogenic	0.9309	pathogenic	-0.1	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
D/E	0.198	likely_benign	0.2448	benign	-0.318	Destabilizing	0.117	N	0.337	neutral	N	0.521383108	None	None	I
D/F	0.8515	likely_pathogenic	0.873	pathogenic	-0.09	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
D/G	0.2335	likely_benign	0.2547	benign	-0.081	Destabilizing	0.989	D	0.68	prob.neutral	D	0.531379809	None	None	I
D/H	0.6491	likely_pathogenic	0.6803	pathogenic	0.461	Stabilizing	0.999	D	0.732	prob.delet.	D	0.548074467	None	None	I
D/I	0.748	likely_pathogenic	0.7809	pathogenic	0.264	Stabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	I
D/K	0.6647	likely_pathogenic	0.6754	pathogenic	0.415	Stabilizing	0.99	D	0.689	prob.neutral	None	None	None	None	I
D/L	0.742	likely_pathogenic	0.7721	pathogenic	0.264	Stabilizing	0.995	D	0.686	prob.neutral	None	None	None	None	I
D/M	0.8478	likely_pathogenic	0.8809	pathogenic	0.077	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
D/N	0.174	likely_benign	0.2007	benign	0.234	Stabilizing	0.993	D	0.73	prob.delet.	N	0.475983161	None	None	I
D/P	0.908	likely_pathogenic	0.9351	pathogenic	0.206	Stabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	I
D/Q	0.5839	likely_pathogenic	0.6211	pathogenic	0.222	Stabilizing	0.99	D	0.727	prob.delet.	None	None	None	None	I
D/R	0.7562	likely_pathogenic	0.7421	pathogenic	0.631	Stabilizing	0.995	D	0.685	prob.neutral	None	None	None	None	I
D/S	0.2813	likely_benign	0.3235	benign	0.129	Stabilizing	0.983	D	0.655	neutral	None	None	None	None	I
D/T	0.5097	ambiguous	0.5548	ambiguous	0.219	Stabilizing	0.995	D	0.704	prob.neutral	None	None	None	None	I
D/V	0.5704	likely_pathogenic	0.5999	pathogenic	0.206	Stabilizing	0.997	D	0.696	prob.neutral	D	0.602708672	None	None	I
D/W	0.965	likely_pathogenic	0.9664	pathogenic	-0.06	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
D/Y	0.5492	ambiguous	0.5454	ambiguous	0.133	Stabilizing	1.0	D	0.729	prob.delet.	D	0.681038194	None	None	I

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.