TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35773	107542;107543;107544	chr2:178528334;178528333;178528332	chr2:179393061;179393060;179393059
N2AB	34132	102619;102620;102621	chr2:178528334;178528333;178528332	chr2:179393061;179393060;179393059
N2A	33205	99838;99839;99840	chr2:178528334;178528333;178528332	chr2:179393061;179393060;179393059
N2B	26708	80347;80348;80349	chr2:178528334;178528333;178528332	chr2:179393061;179393060;179393059
Novex-1	26833	80722;80723;80724	chr2:178528334;178528333;178528332	chr2:179393061;179393060;179393059
Novex-2	26900	80923;80924;80925	chr2:178528334;178528333;178528332	chr2:179393061;179393060;179393059
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-168
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.2233
• 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/K	None	None	1.0	N	0.819	0.371	None	gnomAD-4.0.0	3.1821E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71562E-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	0.1845	likely_benign	0.1801	benign	-1.485	Destabilizing	0.999	D	0.555	neutral	N	0.469876484	None	None	N
T/C	0.7471	likely_pathogenic	0.7876	pathogenic	-0.985	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
T/D	0.806	likely_pathogenic	0.8112	pathogenic	-1.717	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
T/E	0.6233	likely_pathogenic	0.6153	pathogenic	-1.459	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
T/F	0.5206	ambiguous	0.5323	ambiguous	-1.105	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
T/G	0.6234	likely_pathogenic	0.624	pathogenic	-1.91	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
T/H	0.5281	ambiguous	0.5257	ambiguous	-1.81	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
T/I	0.3165	likely_benign	0.317	benign	-0.337	Destabilizing	1.0	D	0.82	deleterious	N	0.506466723	None	None	N
T/K	0.5422	ambiguous	0.5288	ambiguous	-0.281	Destabilizing	1.0	D	0.819	deleterious	N	0.511680542	None	None	N
T/L	0.2518	likely_benign	0.2472	benign	-0.337	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
T/M	0.141	likely_benign	0.1431	benign	-0.512	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
T/N	0.3418	ambiguous	0.339	benign	-1.112	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
T/P	0.9066	likely_pathogenic	0.9049	pathogenic	-0.693	Destabilizing	1.0	D	0.825	deleterious	N	0.514594144	None	None	N
T/Q	0.4452	ambiguous	0.4351	ambiguous	-0.809	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
T/R	0.4082	ambiguous	0.3945	ambiguous	-0.621	Destabilizing	1.0	D	0.835	deleterious	N	0.508736237	None	None	N
T/S	0.2232	likely_benign	0.2196	benign	-1.382	Destabilizing	0.999	D	0.521	neutral	N	0.446244983	None	None	N
T/V	0.2487	likely_benign	0.2489	benign	-0.693	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	N
T/W	0.8563	likely_pathogenic	0.8628	pathogenic	-1.223	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
T/Y	0.6093	likely_pathogenic	0.6144	pathogenic	-0.841	Destabilizing	1.0	D	0.862	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.