TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5384	16375;16376;16377	chr2:178733026;178733025;178733024	chr2:179597753;179597752;179597751
N2AB	5067	15424;15425;15426	chr2:178733026;178733025;178733024	chr2:179597753;179597752;179597751
N2A	4140	12643;12644;12645	chr2:178733026;178733025;178733024	chr2:179597753;179597752;179597751
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-37
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.8274
• 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
L/F	rs879244251	None	0.966	N	0.386	0.323	0.663891511034	gnomAD-4.0.0	6.84362E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99548E-07	0	0
L/V	None	None	0.891	N	0.345	0.218	0.615873902259	gnomAD-4.0.0	6.84362E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99548E-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
L/A	0.2858	likely_benign	0.2436	benign	-0.361	Destabilizing	0.688	D	0.347	neutral	None	None	None	None	I
L/C	0.7477	likely_pathogenic	0.729	pathogenic	-0.706	Destabilizing	0.998	D	0.413	neutral	None	None	None	None	I
L/D	0.7392	likely_pathogenic	0.6929	pathogenic	-0.223	Destabilizing	0.842	D	0.491	neutral	None	None	None	None	I
L/E	0.3901	ambiguous	0.3541	ambiguous	-0.32	Destabilizing	0.728	D	0.386	neutral	None	None	None	None	I
L/F	0.182	likely_benign	0.1583	benign	-0.601	Destabilizing	0.966	D	0.386	neutral	N	0.506891663	None	None	I
L/G	0.6094	likely_pathogenic	0.5723	pathogenic	-0.447	Destabilizing	0.842	D	0.499	neutral	None	None	None	None	I
L/H	0.3004	likely_benign	0.2559	benign	0.121	Stabilizing	0.028	N	0.267	neutral	N	0.488132544	None	None	I
L/I	0.14	likely_benign	0.1296	benign	-0.258	Destabilizing	0.891	D	0.429	neutral	N	0.495674592	None	None	I
L/K	0.3299	likely_benign	0.2969	benign	-0.257	Destabilizing	0.728	D	0.438	neutral	None	None	None	None	I
L/M	0.1556	likely_benign	0.1428	benign	-0.544	Destabilizing	0.991	D	0.404	neutral	None	None	None	None	I
L/N	0.4608	ambiguous	0.4131	ambiguous	-0.082	Destabilizing	0.949	D	0.477	neutral	None	None	None	None	I
L/P	0.2359	likely_benign	0.2066	benign	-0.266	Destabilizing	0.012	N	0.217	neutral	N	0.312363352	None	None	I
L/Q	0.179	likely_benign	0.1508	benign	-0.267	Destabilizing	0.172	N	0.153	neutral	None	None	None	None	I
L/R	0.2523	likely_benign	0.2262	benign	0.178	Stabilizing	0.801	D	0.467	neutral	N	0.50619823	None	None	I
L/S	0.2841	likely_benign	0.2382	benign	-0.448	Destabilizing	0.842	D	0.432	neutral	None	None	None	None	I
L/T	0.3179	likely_benign	0.2694	benign	-0.448	Destabilizing	0.915	D	0.435	neutral	None	None	None	None	I
L/V	0.1296	likely_benign	0.1177	benign	-0.266	Destabilizing	0.891	D	0.345	neutral	N	0.495674592	None	None	I
L/W	0.3682	ambiguous	0.3343	benign	-0.629	Destabilizing	0.998	D	0.43	neutral	None	None	None	None	I
L/Y	0.4218	ambiguous	0.3828	ambiguous	-0.381	Destabilizing	0.949	D	0.452	neutral	None	None	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.