TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21615	65068;65069;65070	chr2:178584798;178584797;178584796	chr2:179449525;179449524;179449523
N2AB	19974	60145;60146;60147	chr2:178584798;178584797;178584796	chr2:179449525;179449524;179449523
N2A	19047	57364;57365;57366	chr2:178584798;178584797;178584796	chr2:179449525;179449524;179449523
N2B	12550	37873;37874;37875	chr2:178584798;178584797;178584796	chr2:179449525;179449524;179449523
Novex-1	12675	38248;38249;38250	chr2:178584798;178584797;178584796	chr2:179449525;179449524;179449523
Novex-2	12742	38449;38450;38451	chr2:178584798;178584797;178584796	chr2:179449525;179449524;179449523
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-44
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.7785
• 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
T/I	None	None	1.0	N	0.647	0.428	0.461934685604	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	3.66327E-05

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
T/A	0.1153	likely_benign	0.1283	benign	-0.491	Destabilizing	0.999	D	0.481	neutral	N	0.431345394	None	None	I
T/C	0.5684	likely_pathogenic	0.5413	ambiguous	-0.385	Destabilizing	1.0	D	0.603	neutral	None	None	None	None	I
T/D	0.7934	likely_pathogenic	0.8255	pathogenic	0.314	Stabilizing	1.0	D	0.654	neutral	None	None	None	None	I
T/E	0.6792	likely_pathogenic	0.7223	pathogenic	0.255	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	I
T/F	0.5672	likely_pathogenic	0.5819	pathogenic	-0.91	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	I
T/G	0.2698	likely_benign	0.2604	benign	-0.642	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	I
T/H	0.51	ambiguous	0.5351	ambiguous	-0.859	Destabilizing	1.0	D	0.608	neutral	None	None	None	None	I
T/I	0.4215	ambiguous	0.4328	ambiguous	-0.207	Destabilizing	1.0	D	0.647	neutral	N	0.470589225	None	None	I
T/K	0.466	ambiguous	0.5117	ambiguous	-0.398	Destabilizing	1.0	D	0.661	neutral	N	0.43159611	None	None	I
T/L	0.191	likely_benign	0.2025	benign	-0.207	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
T/M	0.1467	likely_benign	0.1616	benign	-0.11	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	I
T/N	0.2225	likely_benign	0.2309	benign	-0.245	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
T/P	0.151	likely_benign	0.1616	benign	-0.272	Destabilizing	1.0	D	0.643	neutral	N	0.466284687	None	None	I
T/Q	0.3541	ambiguous	0.3747	ambiguous	-0.431	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
T/R	0.4551	ambiguous	0.5079	ambiguous	-0.133	Destabilizing	1.0	D	0.645	neutral	N	0.464996607	None	None	I
T/S	0.1525	likely_benign	0.1612	benign	-0.501	Destabilizing	0.999	D	0.512	neutral	N	0.42951581	None	None	I
T/V	0.2762	likely_benign	0.2861	benign	-0.272	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	I
T/W	0.8231	likely_pathogenic	0.832	pathogenic	-0.892	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	I
T/Y	0.6113	likely_pathogenic	0.6137	pathogenic	-0.617	Destabilizing	1.0	D	0.638	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.