TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6191	18796;18797;18798	chr2:178729682;178729681;178729680	chr2:179594409;179594408;179594407
N2AB	5874	17845;17846;17847	chr2:178729682;178729681;178729680	chr2:179594409;179594408;179594407
N2A	4947	15064;15065;15066	chr2:178729682;178729681;178729680	chr2:179594409;179594408;179594407
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-45
• Domain position: 87
• Structural Position: 172
• Q(SASA): 0.0817
• 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	rs752079323	-2.661	0.193	N	0.683	0.246	0.482721949076	gnomAD-2.1.1	3.63E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	7.14E-05	1.65948E-04
I/T	rs752079323	-2.661	0.193	N	0.683	0.246	0.482721949076	gnomAD-4.0.0	2.70549E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.88239E-05	0	3.14465E-05	0	1.5124E-04
I/V	None	None	0.001	N	0.123	0.09	0.231873229951	gnomAD-4.0.0	1.59146E-06	None	None	None	None	N	None	0	0	None	4.76872E-05	0	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	0.1448	likely_benign	0.1589	benign	-2.532	Highly Destabilizing	0.116	N	0.633	neutral	None	None	None	None	N
I/C	0.7232	likely_pathogenic	0.7354	pathogenic	-1.866	Destabilizing	0.944	D	0.708	prob.delet.	None	None	None	None	N
I/D	0.8316	likely_pathogenic	0.821	pathogenic	-2.527	Highly Destabilizing	0.818	D	0.789	deleterious	None	None	None	None	N
I/E	0.6755	likely_pathogenic	0.6755	pathogenic	-2.294	Highly Destabilizing	0.818	D	0.798	deleterious	None	None	None	None	N
I/F	0.1928	likely_benign	0.1925	benign	-1.444	Destabilizing	0.627	D	0.723	prob.delet.	N	0.454868119	None	None	N
I/G	0.5773	likely_pathogenic	0.591	pathogenic	-3.102	Highly Destabilizing	0.818	D	0.794	deleterious	None	None	None	None	N
I/H	0.6987	likely_pathogenic	0.701	pathogenic	-2.491	Highly Destabilizing	0.981	D	0.736	prob.delet.	None	None	None	None	N
I/K	0.5793	likely_pathogenic	0.5775	pathogenic	-1.989	Destabilizing	0.818	D	0.796	deleterious	None	None	None	None	N
I/L	0.135	likely_benign	0.1308	benign	-0.888	Destabilizing	0.041	N	0.406	neutral	N	0.463407458	None	None	N
I/M	0.0766	likely_benign	0.0778	benign	-0.856	Destabilizing	0.018	N	0.222	neutral	N	0.471184366	None	None	N
I/N	0.4628	ambiguous	0.4437	ambiguous	-2.277	Highly Destabilizing	0.912	D	0.797	deleterious	D	0.530520671	None	None	N
I/P	0.8725	likely_pathogenic	0.8934	pathogenic	-1.416	Destabilizing	0.932	D	0.797	deleterious	None	None	None	None	N
I/Q	0.5727	likely_pathogenic	0.5786	pathogenic	-2.115	Highly Destabilizing	0.818	D	0.797	deleterious	None	None	None	None	N
I/R	0.4376	ambiguous	0.4459	ambiguous	-1.759	Destabilizing	0.818	D	0.798	deleterious	None	None	None	None	N
I/S	0.2552	likely_benign	0.2596	benign	-3.04	Highly Destabilizing	0.324	N	0.752	deleterious	N	0.424777286	None	None	N
I/T	0.0866	likely_benign	0.0942	benign	-2.644	Highly Destabilizing	0.193	N	0.683	prob.neutral	N	0.38914456	None	None	N
I/V	0.0632	likely_benign	0.0654	benign	-1.416	Destabilizing	0.001	N	0.123	neutral	N	0.442570826	None	None	N
I/W	0.7867	likely_pathogenic	0.803	pathogenic	-1.766	Destabilizing	0.981	D	0.741	deleterious	None	None	None	None	N
I/Y	0.632	likely_pathogenic	0.6375	pathogenic	-1.497	Destabilizing	0.818	D	0.767	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.