TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25322	76189;76190;76191	chr2:178570168;178570167;178570166	chr2:179434895;179434894;179434893
N2AB	23681	71266;71267;71268	chr2:178570168;178570167;178570166	chr2:179434895;179434894;179434893
N2A	22754	68485;68486;68487	chr2:178570168;178570167;178570166	chr2:179434895;179434894;179434893
N2B	16257	48994;48995;48996	chr2:178570168;178570167;178570166	chr2:179434895;179434894;179434893
Novex-1	16382	49369;49370;49371	chr2:178570168;178570167;178570166	chr2:179434895;179434894;179434893
Novex-2	16449	49570;49571;49572	chr2:178570168;178570167;178570166	chr2:179434895;179434894;179434893
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-72
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.2095
• Predicted PPI site: N

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
I/T	None	None	None	N	0.258	0.14	0.319970858106	gnomAD-4.0.0	2.73724E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.5983E-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
I/A	0.474	ambiguous	0.4059	ambiguous	-1.996	Destabilizing	0.035	N	0.397	neutral	None	None	None	None	N
I/C	0.8333	likely_pathogenic	0.8432	pathogenic	-1.371	Destabilizing	0.824	D	0.545	neutral	None	None	None	None	N
I/D	0.9375	likely_pathogenic	0.9188	pathogenic	-1.557	Destabilizing	0.38	N	0.617	neutral	None	None	None	None	N
I/E	0.9036	likely_pathogenic	0.88	pathogenic	-1.518	Destabilizing	0.38	N	0.601	neutral	None	None	None	None	N
I/F	0.4131	ambiguous	0.3798	ambiguous	-1.352	Destabilizing	0.317	N	0.551	neutral	N	0.487177247	None	None	N
I/G	0.8754	likely_pathogenic	0.8593	pathogenic	-2.363	Highly Destabilizing	0.149	N	0.591	neutral	None	None	None	None	N
I/H	0.8471	likely_pathogenic	0.8282	pathogenic	-1.545	Destabilizing	0.935	D	0.634	neutral	None	None	None	None	N
I/K	0.8661	likely_pathogenic	0.8522	pathogenic	-1.418	Destabilizing	0.38	N	0.604	neutral	None	None	None	None	N
I/L	0.2039	likely_benign	0.189	benign	-1.033	Destabilizing	0.012	N	0.378	neutral	N	0.43892194	None	None	N
I/M	0.1367	likely_benign	0.1268	benign	-0.862	Destabilizing	0.317	N	0.559	neutral	N	0.473266587	None	None	N
I/N	0.5706	likely_pathogenic	0.4908	ambiguous	-1.294	Destabilizing	0.317	N	0.625	neutral	N	0.447061421	None	None	N
I/P	0.9746	likely_pathogenic	0.9691	pathogenic	-1.325	Destabilizing	0.555	D	0.621	neutral	None	None	None	None	N
I/Q	0.8321	likely_pathogenic	0.8128	pathogenic	-1.453	Destabilizing	0.555	D	0.645	neutral	None	None	None	None	N
I/R	0.8138	likely_pathogenic	0.7976	pathogenic	-0.836	Destabilizing	0.38	N	0.623	neutral	None	None	None	None	N
I/S	0.5082	ambiguous	0.4224	ambiguous	-1.973	Destabilizing	0.062	N	0.501	neutral	N	0.42835823	None	None	N
I/T	0.1783	likely_benign	0.1297	benign	-1.815	Destabilizing	None	N	0.258	neutral	N	0.324057639	None	None	N
I/V	0.0758	likely_benign	0.0784	benign	-1.325	Destabilizing	None	N	0.197	neutral	N	0.355804698	None	None	N
I/W	0.9206	likely_pathogenic	0.9222	pathogenic	-1.438	Destabilizing	0.935	D	0.668	neutral	None	None	None	None	N
I/Y	0.7969	likely_pathogenic	0.786	pathogenic	-1.228	Destabilizing	0.555	D	0.566	neutral	None	None	None	None	N

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.