TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26526	79801;79802;79803	chr2:178566556;178566555;178566554	chr2:179431283;179431282;179431281
N2AB	24885	74878;74879;74880	chr2:178566556;178566555;178566554	chr2:179431283;179431282;179431281
N2A	23958	72097;72098;72099	chr2:178566556;178566555;178566554	chr2:179431283;179431282;179431281
N2B	17461	52606;52607;52608	chr2:178566556;178566555;178566554	chr2:179431283;179431282;179431281
Novex-1	17586	52981;52982;52983	chr2:178566556;178566555;178566554	chr2:179431283;179431282;179431281
Novex-2	17653	53182;53183;53184	chr2:178566556;178566555;178566554	chr2:179431283;179431282;179431281
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-81
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1285
• 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	0.117	N	0.781	0.322	0.684497691411	gnomAD-4.0.0	3.18506E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.89775E-05	0	2.85871E-06	0	0
I/V	None	None	0.012	N	0.447	0.054	0.343788945184	gnomAD-4.0.0	1.59255E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85869E-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	0.4076	ambiguous	0.3411	ambiguous	-2.124	Highly Destabilizing	0.081	N	0.735	prob.delet.	None	None	None	None	N
I/C	0.6199	likely_pathogenic	0.5723	pathogenic	-1.14	Destabilizing	0.935	D	0.772	deleterious	None	None	None	None	N
I/D	0.8925	likely_pathogenic	0.8434	pathogenic	-2.676	Highly Destabilizing	0.791	D	0.814	deleterious	None	None	None	None	N
I/E	0.7733	likely_pathogenic	0.6946	pathogenic	-2.364	Highly Destabilizing	0.555	D	0.821	deleterious	None	None	None	None	N
I/F	0.1471	likely_benign	0.1401	benign	-1.267	Destabilizing	0.001	N	0.465	neutral	N	0.471938436	None	None	N
I/G	0.7575	likely_pathogenic	0.6949	pathogenic	-2.728	Highly Destabilizing	0.555	D	0.802	deleterious	None	None	None	None	N
I/H	0.6221	likely_pathogenic	0.5543	ambiguous	-2.529	Highly Destabilizing	0.935	D	0.792	deleterious	None	None	None	None	N
I/K	0.4493	ambiguous	0.3734	ambiguous	-1.419	Destabilizing	0.38	N	0.812	deleterious	None	None	None	None	N
I/L	0.107	likely_benign	0.1039	benign	-0.335	Destabilizing	None	N	0.247	neutral	N	0.476016104	None	None	N
I/M	0.0854	likely_benign	0.0834	benign	-0.362	Destabilizing	0.004	N	0.481	neutral	N	0.437961935	None	None	N
I/N	0.4556	ambiguous	0.3752	ambiguous	-2.059	Highly Destabilizing	0.484	N	0.815	deleterious	N	0.489410587	None	None	N
I/P	0.9805	likely_pathogenic	0.9717	pathogenic	-0.918	Destabilizing	0.791	D	0.812	deleterious	None	None	None	None	N
I/Q	0.5938	likely_pathogenic	0.5073	ambiguous	-1.715	Destabilizing	0.555	D	0.812	deleterious	None	None	None	None	N
I/R	0.4124	ambiguous	0.3384	benign	-1.579	Destabilizing	0.38	N	0.82	deleterious	None	None	None	None	N
I/S	0.3958	ambiguous	0.3192	benign	-2.648	Highly Destabilizing	0.317	N	0.779	deleterious	N	0.495258012	None	None	N
I/T	0.2455	likely_benign	0.1747	benign	-2.169	Highly Destabilizing	0.117	N	0.781	deleterious	N	0.480000558	None	None	N
I/V	0.0911	likely_benign	0.0864	benign	-0.918	Destabilizing	0.012	N	0.447	neutral	N	0.446213272	None	None	N
I/W	0.7673	likely_pathogenic	0.7186	pathogenic	-1.741	Destabilizing	0.935	D	0.793	deleterious	None	None	None	None	N
I/Y	0.411	ambiguous	0.3829	ambiguous	-1.375	Destabilizing	0.235	N	0.798	deleterious	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.