TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32260	97003;97004;97005	chr2:178543195;178543194;178543193	chr2:179407922;179407921;179407920
N2AB	30619	92080;92081;92082	chr2:178543195;178543194;178543193	chr2:179407922;179407921;179407920
N2A	29692	89299;89300;89301	chr2:178543195;178543194;178543193	chr2:179407922;179407921;179407920
N2B	23195	69808;69809;69810	chr2:178543195;178543194;178543193	chr2:179407922;179407921;179407920
Novex-1	23320	70183;70184;70185	chr2:178543195;178543194;178543193	chr2:179407922;179407921;179407920
Novex-2	23387	70384;70385;70386	chr2:178543195;178543194;178543193	chr2:179407922;179407921;179407920
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-123
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.2192
• 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
L/V	rs1695466303	None	0.801	N	0.401	0.161	0.408714661073	gnomAD-4.0.0	1.36841E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79893E-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
L/A	0.175	likely_benign	0.1826	benign	-1.789	Destabilizing	0.525	D	0.402	neutral	None	None	None	None	I
L/C	0.3499	ambiguous	0.3512	ambiguous	-0.962	Destabilizing	0.998	D	0.509	neutral	None	None	None	None	I
L/D	0.6239	likely_pathogenic	0.6429	pathogenic	-1.641	Destabilizing	0.949	D	0.589	neutral	None	None	None	None	I
L/E	0.3211	likely_benign	0.3492	ambiguous	-1.476	Destabilizing	0.949	D	0.579	neutral	None	None	None	None	I
L/F	0.1176	likely_benign	0.1225	benign	-1.009	Destabilizing	0.007	N	0.2	neutral	None	None	None	None	I
L/G	0.3244	likely_benign	0.3435	ambiguous	-2.25	Highly Destabilizing	0.842	D	0.503	neutral	None	None	None	None	I
L/H	0.1779	likely_benign	0.201	benign	-1.507	Destabilizing	0.949	D	0.583	neutral	None	None	None	None	I
L/I	0.1405	likely_benign	0.1411	benign	-0.511	Destabilizing	0.669	D	0.388	neutral	N	0.473317341	None	None	I
L/K	0.1752	likely_benign	0.2157	benign	-1.243	Destabilizing	0.842	D	0.556	neutral	None	None	None	None	I
L/M	0.1033	likely_benign	0.1066	benign	-0.403	Destabilizing	0.974	D	0.507	neutral	None	None	None	None	I
L/N	0.2916	likely_benign	0.3207	benign	-1.455	Destabilizing	0.949	D	0.59	neutral	None	None	None	None	I
L/P	0.1767	likely_benign	0.1878	benign	-0.912	Destabilizing	0.966	D	0.583	neutral	N	0.493601787	None	None	I
L/Q	0.1043	likely_benign	0.1207	benign	-1.397	Destabilizing	0.966	D	0.57	neutral	N	0.46729018	None	None	I
L/R	0.122	likely_benign	0.1466	benign	-0.907	Destabilizing	0.966	D	0.568	neutral	N	0.505376219	None	None	I
L/S	0.1973	likely_benign	0.2006	benign	-2.116	Highly Destabilizing	0.172	N	0.411	neutral	None	None	None	None	I
L/T	0.122	likely_benign	0.1256	benign	-1.813	Destabilizing	0.728	D	0.406	neutral	None	None	None	None	I
L/V	0.1101	likely_benign	0.112	benign	-0.912	Destabilizing	0.801	D	0.401	neutral	N	0.471342331	None	None	I
L/W	0.1778	likely_benign	0.1891	benign	-1.306	Destabilizing	0.993	D	0.567	neutral	None	None	None	None	I
L/Y	0.263	likely_benign	0.2861	benign	-0.958	Destabilizing	0.016	N	0.322	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.