TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5237	15934;15935;15936	chr2:178733680;178733679;178733678	chr2:179598407;179598406;179598405
N2AB	4920	14983;14984;14985	chr2:178733680;178733679;178733678	chr2:179598407;179598406;179598405
N2A	3993	12202;12203;12204	chr2:178733680;178733679;178733678	chr2:179598407;179598406;179598405
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-35
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.6949
• 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
K/I	rs2080944134	None	1.0	D	0.762	0.49	0.572964795716	gnomAD-4.0.0	6.84216E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99481E-07	0	0
K/T	None	None	0.999	N	0.757	0.439	0.397691132334	gnomAD-4.0.0	6.84216E-07	None	None	None	None	I	None	2.98775E-05	0	None	0	0	None	0	0	0	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
K/A	0.3049	likely_benign	0.413	ambiguous	-0.201	Destabilizing	0.997	D	0.655	neutral	None	None	None	None	I
K/C	0.6597	likely_pathogenic	0.7604	pathogenic	-0.378	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
K/D	0.4778	ambiguous	0.611	pathogenic	0.376	Stabilizing	0.994	D	0.703	prob.neutral	None	None	None	None	I
K/E	0.1559	likely_benign	0.1875	benign	0.418	Stabilizing	0.767	D	0.367	neutral	N	0.512684565	None	None	I
K/F	0.6563	likely_pathogenic	0.7581	pathogenic	-0.246	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
K/G	0.4293	ambiguous	0.5607	ambiguous	-0.456	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
K/H	0.2553	likely_benign	0.3438	ambiguous	-0.727	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
K/I	0.2498	likely_benign	0.3126	benign	0.405	Stabilizing	1.0	D	0.762	deleterious	D	0.535207842	None	None	I
K/L	0.2874	likely_benign	0.3957	ambiguous	0.405	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
K/M	0.206	likely_benign	0.2485	benign	0.217	Stabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
K/N	0.2931	likely_benign	0.3849	ambiguous	0.12	Stabilizing	0.999	D	0.714	prob.delet.	N	0.505557969	None	None	I
K/P	0.5658	likely_pathogenic	0.7182	pathogenic	0.233	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
K/Q	0.1176	likely_benign	0.1424	benign	-0.039	Destabilizing	0.999	D	0.711	prob.delet.	N	0.513609025	None	None	I
K/R	0.074	likely_benign	0.0833	benign	-0.113	Destabilizing	0.996	D	0.613	neutral	N	0.514740687	None	None	I
K/S	0.318	likely_benign	0.4353	ambiguous	-0.528	Destabilizing	0.997	D	0.646	neutral	None	None	None	None	I
K/T	0.1457	likely_benign	0.1819	benign	-0.31	Destabilizing	0.999	D	0.757	deleterious	N	0.507818426	None	None	I
K/V	0.2689	likely_benign	0.3406	ambiguous	0.233	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
K/W	0.6616	likely_pathogenic	0.7792	pathogenic	-0.158	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
K/Y	0.518	ambiguous	0.6211	pathogenic	0.175	Stabilizing	1.0	D	0.751	deleterious	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.