TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35155	105688;105689;105690	chr2:178531152;178531151;178531150	chr2:179395879;179395878;179395877
N2AB	33514	100765;100766;100767	chr2:178531152;178531151;178531150	chr2:179395879;179395878;179395877
N2A	32587	97984;97985;97986	chr2:178531152;178531151;178531150	chr2:179395879;179395878;179395877
N2B	26090	78493;78494;78495	chr2:178531152;178531151;178531150	chr2:179395879;179395878;179395877
Novex-1	26215	78868;78869;78870	chr2:178531152;178531151;178531150	chr2:179395879;179395878;179395877
Novex-2	26282	79069;79070;79071	chr2:178531152;178531151;178531150	chr2:179395879;179395878;179395877
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-164
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.5381
• 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/K	rs748014260	0.014	0.997	D	0.683	0.454	0.512651460143	gnomAD-2.1.1	8.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
E/K	rs748014260	0.014	0.997	D	0.683	0.454	0.512651460143	gnomAD-4.0.0	6.84135E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.29575E-06	3.47794E-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	0.438	ambiguous	0.5479	ambiguous	-0.119	Destabilizing	0.997	D	0.681	prob.neutral	D	0.523130552	None	None	I
E/C	0.9664	likely_pathogenic	0.9787	pathogenic	-0.142	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
E/D	0.451	ambiguous	0.5957	pathogenic	-0.225	Destabilizing	0.997	D	0.49	neutral	N	0.450403662	None	None	I
E/F	0.8597	likely_pathogenic	0.9058	pathogenic	-0.038	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
E/G	0.6049	likely_pathogenic	0.7354	pathogenic	-0.28	Destabilizing	0.999	D	0.677	prob.neutral	N	0.514979214	None	None	I
E/H	0.8085	likely_pathogenic	0.8763	pathogenic	0.449	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
E/I	0.5509	ambiguous	0.6411	pathogenic	0.258	Stabilizing	0.999	D	0.755	deleterious	None	None	None	None	I
E/K	0.4156	ambiguous	0.5621	ambiguous	0.398	Stabilizing	0.997	D	0.683	prob.neutral	D	0.522957194	None	None	I
E/L	0.6873	likely_pathogenic	0.7737	pathogenic	0.258	Stabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	I
E/M	0.6589	likely_pathogenic	0.7442	pathogenic	0.101	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
E/N	0.64	likely_pathogenic	0.7492	pathogenic	0.114	Stabilizing	0.999	D	0.773	deleterious	None	None	None	None	I
E/P	0.9674	likely_pathogenic	0.988	pathogenic	0.152	Stabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
E/Q	0.3219	likely_benign	0.4239	ambiguous	0.147	Stabilizing	0.999	D	0.669	neutral	D	0.528499086	None	None	I
E/R	0.6308	likely_pathogenic	0.7684	pathogenic	0.664	Stabilizing	0.999	D	0.769	deleterious	None	None	None	None	I
E/S	0.5076	ambiguous	0.6309	pathogenic	-0.05	Destabilizing	0.998	D	0.722	prob.delet.	None	None	None	None	I
E/T	0.5392	ambiguous	0.6619	pathogenic	0.087	Stabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	I
E/V	0.399	ambiguous	0.4915	ambiguous	0.152	Stabilizing	0.999	D	0.733	prob.delet.	D	0.523938629	None	None	I
E/W	0.9734	likely_pathogenic	0.9864	pathogenic	0.061	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
E/Y	0.8325	likely_pathogenic	0.89	pathogenic	0.199	Stabilizing	1.0	D	0.742	deleterious	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.