TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13826	41701;41702;41703	chr2:178636095;178636094;178636093	chr2:179500822;179500821;179500820
N2AB	12185	36778;36779;36780	chr2:178636095;178636094;178636093	chr2:179500822;179500821;179500820
N2A	11258	33997;33998;33999	chr2:178636095;178636094;178636093	chr2:179500822;179500821;179500820
N2B	4761	14506;14507;14508	chr2:178636095;178636094;178636093	chr2:179500822;179500821;179500820
Novex-1	4886	14881;14882;14883	chr2:178636095;178636094;178636093	chr2:179500822;179500821;179500820
Novex-2	4953	15082;15083;15084	chr2:178636095;178636094;178636093	chr2:179500822;179500821;179500820
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-88
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.081
• 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/N	rs1252440805	None	0.772	N	0.741	0.138	0.389439708392	gnomAD-4.0.0	6.84415E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9964E-07	0	0
I/T	rs1252440805	-3.055	0.003	N	0.427	0.149	0.354396617058	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	9.29E-05	0	0
I/V	None	None	0.001	N	0.171	0.082	0.170165803431	gnomAD-4.0.0	1.59242E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86005E-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	0.5809	likely_pathogenic	0.6923	pathogenic	-2.622	Highly Destabilizing	0.209	N	0.634	neutral	None	None	None	None	N
I/C	0.8393	likely_pathogenic	0.8568	pathogenic	-1.923	Destabilizing	0.965	D	0.578	neutral	None	None	None	None	N
I/D	0.9232	likely_pathogenic	0.95	pathogenic	-2.98	Highly Destabilizing	0.818	D	0.735	deleterious	None	None	None	None	N
I/E	0.8346	likely_pathogenic	0.8837	pathogenic	-2.844	Highly Destabilizing	0.561	D	0.7	prob.delet.	None	None	None	None	N
I/F	0.2199	likely_benign	0.2455	benign	-1.63	Destabilizing	0.003	N	0.353	neutral	N	0.346905246	None	None	N
I/G	0.8916	likely_pathogenic	0.9317	pathogenic	-3.087	Highly Destabilizing	0.561	D	0.669	prob.neutral	None	None	None	None	N
I/H	0.7983	likely_pathogenic	0.8248	pathogenic	-2.46	Highly Destabilizing	0.818	D	0.691	prob.delet.	None	None	None	None	N
I/K	0.7832	likely_pathogenic	0.8261	pathogenic	-2.185	Highly Destabilizing	0.561	D	0.701	prob.delet.	None	None	None	None	N
I/L	0.1987	likely_benign	0.2289	benign	-1.31	Destabilizing	None	N	0.175	neutral	N	0.339451123	None	None	N
I/M	0.1522	likely_benign	0.1632	benign	-1.172	Destabilizing	0.772	D	0.531	neutral	N	0.32862299	None	None	N
I/N	0.6295	likely_pathogenic	0.6902	pathogenic	-2.285	Highly Destabilizing	0.772	D	0.741	deleterious	N	0.309993656	None	None	N
I/P	0.9436	likely_pathogenic	0.9647	pathogenic	-1.726	Destabilizing	0.901	D	0.726	deleterious	None	None	None	None	N
I/Q	0.7944	likely_pathogenic	0.8305	pathogenic	-2.301	Highly Destabilizing	0.901	D	0.714	prob.delet.	None	None	None	None	N
I/R	0.6808	likely_pathogenic	0.7395	pathogenic	-1.659	Destabilizing	0.818	D	0.725	deleterious	None	None	None	None	N
I/S	0.6234	likely_pathogenic	0.7074	pathogenic	-2.906	Highly Destabilizing	0.326	N	0.657	prob.neutral	N	0.347693417	None	None	N
I/T	0.3334	likely_benign	0.4379	ambiguous	-2.649	Highly Destabilizing	0.003	N	0.427	neutral	N	0.308566076	None	None	N
I/V	0.091	likely_benign	0.1251	benign	-1.726	Destabilizing	0.001	N	0.171	neutral	N	0.346810489	None	None	N
I/W	0.8441	likely_pathogenic	0.8533	pathogenic	-1.961	Destabilizing	0.972	D	0.691	prob.delet.	None	None	None	None	N
I/Y	0.64	likely_pathogenic	0.6247	pathogenic	-1.75	Destabilizing	0.004	N	0.493	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.