TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20565	61918;61919;61920	chr2:178590032;178590031;178590030	chr2:179454759;179454758;179454757
N2AB	18924	56995;56996;56997	chr2:178590032;178590031;178590030	chr2:179454759;179454758;179454757
N2A	17997	54214;54215;54216	chr2:178590032;178590031;178590030	chr2:179454759;179454758;179454757
N2B	11500	34723;34724;34725	chr2:178590032;178590031;178590030	chr2:179454759;179454758;179454757
Novex-1	11625	35098;35099;35100	chr2:178590032;178590031;178590030	chr2:179454759;179454758;179454757
Novex-2	11692	35299;35300;35301	chr2:178590032;178590031;178590030	chr2:179454759;179454758;179454757
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-121
• Domain position: 87
• Structural Position: 175
• Q(SASA): 0.2678
• 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/K	None	None	1.0	N	0.741	0.343	0.24896430686	gnomAD-4.0.0	6.84484E-07	None	None	None	None	I	None	2.99061E-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
N/A	0.578	likely_pathogenic	0.5989	pathogenic	-0.893	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
N/C	0.497	ambiguous	0.5316	ambiguous	-0.094	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
N/D	0.4656	ambiguous	0.4681	ambiguous	-0.569	Destabilizing	0.999	D	0.605	neutral	N	0.498002821	None	None	I
N/E	0.7532	likely_pathogenic	0.7461	pathogenic	-0.463	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	I
N/F	0.8204	likely_pathogenic	0.8259	pathogenic	-0.528	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
N/G	0.7349	likely_pathogenic	0.7654	pathogenic	-1.243	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	I
N/H	0.162	likely_benign	0.1716	benign	-0.89	Destabilizing	1.0	D	0.735	prob.delet.	N	0.500773767	None	None	I
N/I	0.4792	ambiguous	0.4939	ambiguous	0.002	Stabilizing	1.0	D	0.799	deleterious	N	0.489113979	None	None	I
N/K	0.7033	likely_pathogenic	0.7096	pathogenic	-0.362	Destabilizing	1.0	D	0.741	deleterious	N	0.457769565	None	None	I
N/L	0.4655	ambiguous	0.4671	ambiguous	0.002	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
N/M	0.5669	likely_pathogenic	0.5774	pathogenic	0.367	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
N/P	0.9852	likely_pathogenic	0.9868	pathogenic	-0.267	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
N/Q	0.6103	likely_pathogenic	0.6201	pathogenic	-0.927	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
N/R	0.6792	likely_pathogenic	0.6886	pathogenic	-0.384	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
N/S	0.1564	likely_benign	0.1677	benign	-1.0	Destabilizing	0.999	D	0.566	neutral	N	0.481243857	None	None	I
N/T	0.2171	likely_benign	0.2241	benign	-0.704	Destabilizing	0.999	D	0.72	prob.delet.	N	0.452113029	None	None	I
N/V	0.457	ambiguous	0.4778	ambiguous	-0.267	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
N/W	0.9235	likely_pathogenic	0.9302	pathogenic	-0.267	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
N/Y	0.3554	ambiguous	0.358	ambiguous	-0.076	Destabilizing	1.0	D	0.784	deleterious	N	0.518628809	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.