TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18396	55411;55412;55413	chr2:178602085;178602084;178602083	chr2:179466812;179466811;179466810
N2AB	16755	50488;50489;50490	chr2:178602085;178602084;178602083	chr2:179466812;179466811;179466810
N2A	15828	47707;47708;47709	chr2:178602085;178602084;178602083	chr2:179466812;179466811;179466810
N2B	9331	28216;28217;28218	chr2:178602085;178602084;178602083	chr2:179466812;179466811;179466810
Novex-1	9456	28591;28592;28593	chr2:178602085;178602084;178602083	chr2:179466812;179466811;179466810
Novex-2	9523	28792;28793;28794	chr2:178602085;178602084;178602083	chr2:179466812;179466811;179466810
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: Ig-115
• Domain position: 15
• Structural Position: 28
• Q(SASA): 0.178
• 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
I/V	None	None	None	N	0.185	0.064	0.294918367191	gnomAD-4.0.0	1.59353E-06	None	None	None	None	I	None	0	0	None	0	2.78272E-05	None	0	0	0	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	0.9591	likely_pathogenic	0.9535	pathogenic	-2.952	Highly Destabilizing	0.157	N	0.608	neutral	None	None	None	None	I
I/C	0.9511	likely_pathogenic	0.9422	pathogenic	-2.319	Highly Destabilizing	0.909	D	0.681	prob.neutral	None	None	None	None	I
I/D	0.9988	likely_pathogenic	0.9989	pathogenic	-3.535	Highly Destabilizing	0.726	D	0.779	deleterious	None	None	None	None	I
I/E	0.9963	likely_pathogenic	0.9963	pathogenic	-3.301	Highly Destabilizing	0.726	D	0.775	deleterious	None	None	None	None	I
I/F	0.4452	ambiguous	0.4403	ambiguous	-1.851	Destabilizing	0.002	N	0.294	neutral	N	0.5097736	None	None	I
I/G	0.9914	likely_pathogenic	0.9908	pathogenic	-3.518	Highly Destabilizing	0.726	D	0.765	deleterious	None	None	None	None	I
I/H	0.9931	likely_pathogenic	0.9931	pathogenic	-2.943	Highly Destabilizing	0.968	D	0.754	deleterious	None	None	None	None	I
I/K	0.9914	likely_pathogenic	0.9911	pathogenic	-2.564	Highly Destabilizing	0.726	D	0.779	deleterious	None	None	None	None	I
I/L	0.2157	likely_benign	0.1963	benign	-1.299	Destabilizing	0.025	N	0.385	neutral	N	0.437697284	None	None	I
I/M	0.2332	likely_benign	0.2296	benign	-1.18	Destabilizing	0.497	N	0.597	neutral	N	0.460833902	None	None	I
I/N	0.9831	likely_pathogenic	0.9853	pathogenic	-2.957	Highly Destabilizing	0.859	D	0.777	deleterious	N	0.479445136	None	None	I
I/P	0.9959	likely_pathogenic	0.9961	pathogenic	-1.833	Destabilizing	0.89	D	0.781	deleterious	None	None	None	None	I
I/Q	0.9892	likely_pathogenic	0.9889	pathogenic	-2.821	Highly Destabilizing	0.89	D	0.771	deleterious	None	None	None	None	I
I/R	0.9873	likely_pathogenic	0.9866	pathogenic	-2.156	Highly Destabilizing	0.726	D	0.772	deleterious	None	None	None	None	I
I/S	0.9842	likely_pathogenic	0.9847	pathogenic	-3.63	Highly Destabilizing	0.497	N	0.735	prob.delet.	N	0.479191647	None	None	I
I/T	0.9762	likely_pathogenic	0.9742	pathogenic	-3.247	Highly Destabilizing	0.124	N	0.691	prob.neutral	N	0.467328362	None	None	I
I/V	0.203	likely_benign	0.1821	benign	-1.833	Destabilizing	None	N	0.185	neutral	N	0.470729635	None	None	I
I/W	0.983	likely_pathogenic	0.9829	pathogenic	-2.286	Highly Destabilizing	0.968	D	0.757	deleterious	None	None	None	None	I
I/Y	0.9303	likely_pathogenic	0.9338	pathogenic	-2.038	Highly Destabilizing	0.396	N	0.712	prob.delet.	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.