TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30985	93178;93179;93180	chr2:178548673;178548672;178548671	chr2:179413400;179413399;179413398
N2AB	29344	88255;88256;88257	chr2:178548673;178548672;178548671	chr2:179413400;179413399;179413398
N2A	28417	85474;85475;85476	chr2:178548673;178548672;178548671	chr2:179413400;179413399;179413398
N2B	21920	65983;65984;65985	chr2:178548673;178548672;178548671	chr2:179413400;179413399;179413398
Novex-1	22045	66358;66359;66360	chr2:178548673;178548672;178548671	chr2:179413400;179413399;179413398
Novex-2	22112	66559;66560;66561	chr2:178548673;178548672;178548671	chr2:179413400;179413399;179413398
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-150
• Domain position: 59
• Structural Position: 143
• Q(SASA): 0.4708
• 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/T	rs748877597	0.283	0.801	N	0.367	0.135	0.262175524916	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	9.8E-05	None	0	0	0
N/T	rs748877597	0.283	0.801	N	0.367	0.135	0.262175524916	gnomAD-4.0.0	2.73676E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	4.63725E-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
N/A	0.2545	likely_benign	0.2817	benign	-0.313	Destabilizing	0.842	D	0.381	neutral	None	None	None	None	I
N/C	0.3401	ambiguous	0.3615	ambiguous	0.504	Stabilizing	0.998	D	0.541	neutral	None	None	None	None	I
N/D	0.1156	likely_benign	0.1314	benign	-0.233	Destabilizing	0.012	N	0.284	neutral	N	0.441356452	None	None	I
N/E	0.3241	likely_benign	0.3426	ambiguous	-0.288	Destabilizing	0.016	N	0.327	neutral	None	None	None	None	I
N/F	0.5329	ambiguous	0.5919	pathogenic	-0.822	Destabilizing	0.991	D	0.484	neutral	None	None	None	None	I
N/G	0.2911	likely_benign	0.2985	benign	-0.448	Destabilizing	0.007	N	0.202	neutral	None	None	None	None	I
N/H	0.1276	likely_benign	0.1385	benign	-0.616	Destabilizing	0.966	D	0.419	neutral	N	0.468648716	None	None	I
N/I	0.3008	likely_benign	0.3422	ambiguous	-0.046	Destabilizing	0.966	D	0.481	neutral	N	0.458306369	None	None	I
N/K	0.2708	likely_benign	0.2771	benign	0.241	Stabilizing	0.669	D	0.325	neutral	N	0.428581942	None	None	I
N/L	0.328	likely_benign	0.3496	ambiguous	-0.046	Destabilizing	0.949	D	0.444	neutral	None	None	None	None	I
N/M	0.3606	ambiguous	0.3881	ambiguous	0.557	Stabilizing	0.998	D	0.469	neutral	None	None	None	None	I
N/P	0.7608	likely_pathogenic	0.8014	pathogenic	-0.111	Destabilizing	0.974	D	0.451	neutral	None	None	None	None	I
N/Q	0.2951	likely_benign	0.3075	benign	-0.279	Destabilizing	0.904	D	0.369	neutral	None	None	None	None	I
N/R	0.3574	ambiguous	0.3708	ambiguous	0.379	Stabilizing	0.949	D	0.367	neutral	None	None	None	None	I
N/S	0.1222	likely_benign	0.1291	benign	0.073	Stabilizing	0.625	D	0.383	neutral	N	0.432987684	None	None	I
N/T	0.1787	likely_benign	0.1981	benign	0.139	Stabilizing	0.801	D	0.367	neutral	N	0.469815276	None	None	I
N/V	0.3037	likely_benign	0.3408	ambiguous	-0.111	Destabilizing	0.974	D	0.459	neutral	None	None	None	None	I
N/W	0.7739	likely_pathogenic	0.8045	pathogenic	-0.819	Destabilizing	0.998	D	0.601	neutral	None	None	None	None	I
N/Y	0.1613	likely_benign	0.1813	benign	-0.53	Destabilizing	0.989	D	0.463	neutral	N	0.509488385	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.