TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7025	21298;21299;21300	chr2:178724302;178724301;178724300	chr2:179589029;179589028;179589027
N2AB	6708	20347;20348;20349	chr2:178724302;178724301;178724300	chr2:179589029;179589028;179589027
N2A	5781	17566;17567;17568	chr2:178724302;178724301;178724300	chr2:179589029;179589028;179589027
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-54
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.9367
• 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
N/S	rs2078960594	None	0.166	N	0.358	0.215	0.146414634003	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/S	rs2078960594	None	0.166	N	0.358	0.215	0.146414634003	gnomAD-4.0.0	6.57324E-06	None	None	None	None	I	None	2.41243E-05	0	None	0	0	None	0	0	0	0	0
N/Y	None	None	0.629	N	0.295	0.299	0.521173705876	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
N/A	0.1345	likely_benign	0.13	benign	-0.122	Destabilizing	0.017	N	0.175	neutral	None	None	None	None	I
N/C	0.2984	likely_benign	0.3123	benign	0.159	Stabilizing	0.991	D	0.233	neutral	None	None	None	None	I
N/D	0.0845	likely_benign	0.0741	benign	-0.023	Destabilizing	0.001	N	0.13	neutral	N	0.41909932	None	None	I
N/E	0.2073	likely_benign	0.1867	benign	-0.093	Destabilizing	0.017	N	0.183	neutral	None	None	None	None	I
N/F	0.4715	ambiguous	0.4863	ambiguous	-0.743	Destabilizing	0.818	D	0.258	neutral	None	None	None	None	I
N/G	0.2141	likely_benign	0.2124	benign	-0.199	Destabilizing	0.345	N	0.333	neutral	None	None	None	None	I
N/H	0.0929	likely_benign	0.0914	benign	-0.253	Destabilizing	0.007	N	0.239	neutral	N	0.466834552	None	None	I
N/I	0.1652	likely_benign	0.1673	benign	-0.015	Destabilizing	0.003	N	0.263	neutral	N	0.435146208	None	None	I
N/K	0.1717	likely_benign	0.1654	benign	0.079	Stabilizing	0.491	N	0.289	neutral	N	0.391758003	None	None	I
N/L	0.1859	likely_benign	0.1971	benign	-0.015	Destabilizing	0.209	N	0.291	neutral	None	None	None	None	I
N/M	0.2715	likely_benign	0.2745	benign	0.118	Stabilizing	0.818	D	0.275	neutral	None	None	None	None	I
N/P	0.2964	likely_benign	0.2962	benign	-0.029	Destabilizing	0.722	D	0.304	neutral	None	None	None	None	I
N/Q	0.2206	likely_benign	0.2126	benign	-0.285	Destabilizing	0.561	D	0.253	neutral	None	None	None	None	I
N/R	0.185	likely_benign	0.1949	benign	0.151	Stabilizing	0.561	D	0.263	neutral	None	None	None	None	I
N/S	0.0691	likely_benign	0.0687	benign	-0.034	Destabilizing	0.166	N	0.358	neutral	N	0.399470623	None	None	I
N/T	0.0961	likely_benign	0.0941	benign	None	Stabilizing	0.491	N	0.287	neutral	N	0.429334957	None	None	I
N/V	0.1641	likely_benign	0.1643	benign	-0.029	Destabilizing	0.083	N	0.294	neutral	None	None	None	None	I
N/W	0.7337	likely_pathogenic	0.7345	pathogenic	-0.881	Destabilizing	0.991	D	0.269	neutral	None	None	None	None	I
N/Y	0.165	likely_benign	0.1738	benign	-0.56	Destabilizing	0.629	D	0.295	neutral	N	0.496464026	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.