TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1609	5050;5051;5052	chr2:178777039;178777038;178777037	chr2:179641766;179641765;179641764
N2AB	1609	5050;5051;5052	chr2:178777039;178777038;178777037	chr2:179641766;179641765;179641764
N2A	1609	5050;5051;5052	chr2:178777039;178777038;178777037	chr2:179641766;179641765;179641764
N2B	1563	4912;4913;4914	chr2:178777039;178777038;178777037	chr2:179641766;179641765;179641764
Novex-1	1563	4912;4913;4914	chr2:178777039;178777038;178777037	chr2:179641766;179641765;179641764
Novex-2	1563	4912;4913;4914	chr2:178777039;178777038;178777037	chr2:179641766;179641765;179641764
Novex-3	1609	5050;5051;5052	chr2:178777039;178777038;178777037	chr2:179641766;179641765;179641764

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-7
• Domain position: 54
• Structural Position: 130
• Q(SASA): 0.5045
• 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	0.949	N	0.417	0.126	0.195762928549	gnomAD-4.0.0	6.84137E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99321E-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	0.076	likely_benign	0.0699	benign	-0.189	Destabilizing	0.003	N	0.122	neutral	N	0.450085704	None	None	N
T/C	0.3901	ambiguous	0.368	ambiguous	-0.301	Destabilizing	0.989	D	0.474	neutral	None	None	None	None	N
T/D	0.2891	likely_benign	0.2485	benign	0.141	Stabilizing	0.961	D	0.405	neutral	None	None	None	None	N
T/E	0.2249	likely_benign	0.1917	benign	0.047	Stabilizing	0.923	D	0.403	neutral	None	None	None	None	N
T/F	0.1835	likely_benign	0.1697	benign	-0.843	Destabilizing	0.923	D	0.525	neutral	None	None	None	None	N
T/G	0.1504	likely_benign	0.1371	benign	-0.25	Destabilizing	0.633	D	0.45	neutral	None	None	None	None	N
T/H	0.2343	likely_benign	0.2099	benign	-0.468	Destabilizing	0.996	D	0.569	neutral	None	None	None	None	N
T/I	0.0991	likely_benign	0.0963	benign	-0.153	Destabilizing	0.018	N	0.25	neutral	N	0.451530256	None	None	N
T/K	0.1643	likely_benign	0.1396	benign	-0.229	Destabilizing	0.923	D	0.4	neutral	None	None	None	None	N
T/L	0.0825	likely_benign	0.0792	benign	-0.153	Destabilizing	0.197	N	0.407	neutral	None	None	None	None	N
T/M	0.0824	likely_benign	0.0792	benign	-0.097	Destabilizing	0.979	D	0.463	neutral	None	None	None	None	N
T/N	0.0904	likely_benign	0.0851	benign	-0.026	Destabilizing	0.949	D	0.417	neutral	N	0.446549199	None	None	N
T/P	0.1907	likely_benign	0.154	benign	-0.14	Destabilizing	0.949	D	0.451	neutral	N	0.453534179	None	None	N
T/Q	0.1776	likely_benign	0.1567	benign	-0.242	Destabilizing	0.961	D	0.437	neutral	None	None	None	None	N
T/R	0.143	likely_benign	0.1214	benign	0.026	Stabilizing	0.923	D	0.446	neutral	None	None	None	None	N
T/S	0.0906	likely_benign	0.086	benign	-0.206	Destabilizing	0.565	D	0.399	neutral	N	0.447215533	None	None	N
T/V	0.0888	likely_benign	0.0851	benign	-0.14	Destabilizing	0.197	N	0.401	neutral	None	None	None	None	N
T/W	0.5587	ambiguous	0.511	ambiguous	-0.911	Destabilizing	0.996	D	0.609	neutral	None	None	None	None	N
T/Y	0.295	likely_benign	0.2673	benign	-0.591	Destabilizing	0.961	D	0.546	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.