TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28967	87124;87125;87126	chr2:178558560;178558559;178558558	chr2:179423287;179423286;179423285
N2AB	27326	82201;82202;82203	chr2:178558560;178558559;178558558	chr2:179423287;179423286;179423285
N2A	26399	79420;79421;79422	chr2:178558560;178558559;178558558	chr2:179423287;179423286;179423285
N2B	19902	59929;59930;59931	chr2:178558560;178558559;178558558	chr2:179423287;179423286;179423285
Novex-1	20027	60304;60305;60306	chr2:178558560;178558559;178558558	chr2:179423287;179423286;179423285
Novex-2	20094	60505;60506;60507	chr2:178558560;178558559;178558558	chr2:179423287;179423286;179423285
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-99
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.8105
• 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
E/K	None	None	0.812	N	0.586	0.297	0.314716216878	gnomAD-4.0.0	3.1828E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.8659E-05	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
E/A	0.147	likely_benign	0.1444	benign	-0.19	Destabilizing	0.7	D	0.569	neutral	N	0.468687487	None	None	I
E/C	0.8367	likely_pathogenic	0.8528	pathogenic	-0.161	Destabilizing	0.996	D	0.738	prob.delet.	None	None	None	None	I
E/D	0.133	likely_benign	0.1599	benign	-0.23	Destabilizing	None	N	0.223	neutral	N	0.446216059	None	None	I
E/F	0.7268	likely_pathogenic	0.7651	pathogenic	-0.186	Destabilizing	0.998	D	0.673	neutral	None	None	None	None	I
E/G	0.1824	likely_benign	0.1997	benign	-0.332	Destabilizing	0.886	D	0.47	neutral	N	0.512979768	None	None	I
E/H	0.4992	ambiguous	0.5409	ambiguous	0.296	Stabilizing	0.997	D	0.647	neutral	None	None	None	None	I
E/I	0.2803	likely_benign	0.3025	benign	0.132	Stabilizing	0.95	D	0.69	prob.neutral	None	None	None	None	I
E/K	0.1598	likely_benign	0.1667	benign	0.314	Stabilizing	0.812	D	0.586	neutral	N	0.441327527	None	None	I
E/L	0.3153	likely_benign	0.3314	benign	0.132	Stabilizing	0.95	D	0.68	prob.neutral	None	None	None	None	I
E/M	0.422	ambiguous	0.4324	ambiguous	0.014	Stabilizing	0.975	D	0.643	neutral	None	None	None	None	I
E/N	0.2799	likely_benign	0.324	benign	0.122	Stabilizing	0.686	D	0.581	neutral	None	None	None	None	I
E/P	0.5155	ambiguous	0.5311	ambiguous	0.043	Stabilizing	0.739	D	0.615	neutral	None	None	None	None	I
E/Q	0.1448	likely_benign	0.1486	benign	0.131	Stabilizing	0.957	D	0.577	neutral	N	0.495490086	None	None	I
E/R	0.2773	likely_benign	0.2922	benign	0.558	Stabilizing	0.976	D	0.653	neutral	None	None	None	None	I
E/S	0.1977	likely_benign	0.2157	benign	-0.056	Destabilizing	0.756	D	0.587	neutral	None	None	None	None	I
E/T	0.2281	likely_benign	0.2407	benign	0.06	Stabilizing	0.968	D	0.537	neutral	None	None	None	None	I
E/V	0.1786	likely_benign	0.1922	benign	0.043	Stabilizing	0.911	D	0.627	neutral	N	0.504186927	None	None	I
E/W	0.8939	likely_pathogenic	0.9157	pathogenic	-0.102	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	I
E/Y	0.6409	likely_pathogenic	0.6932	pathogenic	0.04	Stabilizing	0.999	D	0.635	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.