TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33241	99946;99947;99948	chr2:178537486;178537485;178537484	chr2:179402213;179402212;179402211
N2AB	31600	95023;95024;95025	chr2:178537486;178537485;178537484	chr2:179402213;179402212;179402211
N2A	30673	92242;92243;92244	chr2:178537486;178537485;178537484	chr2:179402213;179402212;179402211
N2B	24176	72751;72752;72753	chr2:178537486;178537485;178537484	chr2:179402213;179402212;179402211
Novex-1	24301	73126;73127;73128	chr2:178537486;178537485;178537484	chr2:179402213;179402212;179402211
Novex-2	24368	73327;73328;73329	chr2:178537486;178537485;178537484	chr2:179402213;179402212;179402211
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: Ig-157
• Domain position: 39
• Structural Position: 109
• Q(SASA): 0.5506
• 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
E/K	rs1318192796	0.75	0.996	N	0.579	0.395	0.293147016451	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs1318192796	0.75	0.996	N	0.579	0.395	0.293147016451	gnomAD-4.0.0	3.18324E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86623E-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
E/A	0.1901	likely_benign	0.1811	benign	-0.01	Destabilizing	0.992	D	0.564	neutral	N	0.50817609	None	None	N
E/C	0.9102	likely_pathogenic	0.9059	pathogenic	-0.158	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/D	0.1104	likely_benign	0.1022	benign	-0.34	Destabilizing	0.941	D	0.455	neutral	N	0.467732189	None	None	N
E/F	0.866	likely_pathogenic	0.8932	pathogenic	-0.102	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/G	0.1554	likely_benign	0.153	benign	-0.099	Destabilizing	0.999	D	0.571	neutral	N	0.495225435	None	None	N
E/H	0.5731	likely_pathogenic	0.5567	ambiguous	0.481	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/I	0.5535	ambiguous	0.565	pathogenic	0.165	Stabilizing	0.998	D	0.702	prob.neutral	None	None	None	None	N
E/K	0.1459	likely_benign	0.1397	benign	0.401	Stabilizing	0.996	D	0.579	neutral	N	0.501807478	None	None	N
E/L	0.5915	likely_pathogenic	0.5948	pathogenic	0.165	Stabilizing	0.998	D	0.665	neutral	None	None	None	None	N
E/M	0.6611	likely_pathogenic	0.6662	pathogenic	-0.006	Destabilizing	0.997	D	0.657	neutral	None	None	None	None	N
E/N	0.2748	likely_benign	0.2582	benign	0.208	Stabilizing	0.996	D	0.675	neutral	None	None	None	None	N
E/P	0.3694	ambiguous	0.3573	ambiguous	0.123	Stabilizing	0.987	D	0.623	neutral	None	None	None	None	N
E/Q	0.1987	likely_benign	0.1856	benign	0.209	Stabilizing	0.998	D	0.573	neutral	N	0.508696164	None	None	N
E/R	0.2795	likely_benign	0.2761	benign	0.57	Stabilizing	0.999	D	0.669	neutral	None	None	None	None	N
E/S	0.2184	likely_benign	0.2096	benign	0.073	Stabilizing	0.994	D	0.577	neutral	None	None	None	None	N
E/T	0.2945	likely_benign	0.2928	benign	0.158	Stabilizing	0.999	D	0.607	neutral	None	None	None	None	N
E/V	0.3583	ambiguous	0.3671	ambiguous	0.123	Stabilizing	0.996	D	0.617	neutral	N	0.471785361	None	None	N
E/W	0.9314	likely_pathogenic	0.9381	pathogenic	-0.082	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/Y	0.7646	likely_pathogenic	0.782	pathogenic	0.109	Stabilizing	1.0	D	0.651	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.