TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19209	57850;57851;57852	chr2:178595729;178595728;178595727	chr2:179460456;179460455;179460454
N2AB	17568	52927;52928;52929	chr2:178595729;178595728;178595727	chr2:179460456;179460455;179460454
N2A	16641	50146;50147;50148	chr2:178595729;178595728;178595727	chr2:179460456;179460455;179460454
N2B	10144	30655;30656;30657	chr2:178595729;178595728;178595727	chr2:179460456;179460455;179460454
Novex-1	10269	31030;31031;31032	chr2:178595729;178595728;178595727	chr2:179460456;179460455;179460454
Novex-2	10336	31231;31232;31233	chr2:178595729;178595728;178595727	chr2:179460456;179460455;179460454
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: Fn3-27
• Domain position: 27
• Structural Position: 28
• Q(SASA): 0.9425
• 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/D	rs769829057	-0.019	0.006	N	0.3	0.083	0.266385636622	gnomAD-2.1.1	8.29E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.83E-05	0
E/D	rs769829057	-0.019	0.006	N	0.3	0.083	0.266385636622	gnomAD-4.0.0	4.80402E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.30643E-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
E/A	0.1159	likely_benign	0.125	benign	-0.006	Destabilizing	0.822	D	0.599	neutral	N	0.465724539	None	None	I
E/C	0.7624	likely_pathogenic	0.807	pathogenic	-0.068	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	I
E/D	0.1071	likely_benign	0.1107	benign	-0.26	Destabilizing	0.006	N	0.3	neutral	N	0.46237759	None	None	I
E/F	0.6963	likely_pathogenic	0.7552	pathogenic	-0.073	Destabilizing	0.998	D	0.671	neutral	None	None	None	None	I
E/G	0.1602	likely_benign	0.183	benign	-0.122	Destabilizing	0.822	D	0.512	neutral	N	0.484158371	None	None	I
E/H	0.3781	ambiguous	0.4079	ambiguous	0.451	Stabilizing	0.998	D	0.668	neutral	None	None	None	None	I
E/I	0.2562	likely_benign	0.2999	benign	0.239	Stabilizing	0.978	D	0.689	prob.neutral	None	None	None	None	I
E/K	0.102	likely_benign	0.1216	benign	0.488	Stabilizing	0.822	D	0.626	neutral	N	0.432977403	None	None	I
E/L	0.275	likely_benign	0.3209	benign	0.239	Stabilizing	0.978	D	0.685	prob.neutral	None	None	None	None	I
E/M	0.3648	ambiguous	0.4131	ambiguous	0.075	Stabilizing	0.998	D	0.647	neutral	None	None	None	None	I
E/N	0.2025	likely_benign	0.2228	benign	0.283	Stabilizing	0.915	D	0.618	neutral	None	None	None	None	I
E/P	0.4225	ambiguous	0.4828	ambiguous	0.176	Stabilizing	0.978	D	0.631	neutral	None	None	None	None	I
E/Q	0.1173	likely_benign	0.1236	benign	0.287	Stabilizing	0.942	D	0.607	neutral	N	0.48283022	None	None	I
E/R	0.1855	likely_benign	0.212	benign	0.666	Stabilizing	0.978	D	0.673	neutral	None	None	None	None	I
E/S	0.1562	likely_benign	0.1672	benign	0.14	Stabilizing	0.86	D	0.627	neutral	None	None	None	None	I
E/T	0.1682	likely_benign	0.1888	benign	0.241	Stabilizing	0.956	D	0.565	neutral	None	None	None	None	I
E/V	0.1562	likely_benign	0.1821	benign	0.176	Stabilizing	0.971	D	0.642	neutral	N	0.490180267	None	None	I
E/W	0.8369	likely_pathogenic	0.8784	pathogenic	-0.035	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	I
E/Y	0.5564	ambiguous	0.6225	pathogenic	0.151	Stabilizing	0.998	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.