TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33642	101149;101150;101151	chr2:178535691;178535690;178535689	chr2:179400418;179400417;179400416
N2AB	32001	96226;96227;96228	chr2:178535691;178535690;178535689	chr2:179400418;179400417;179400416
N2A	31074	93445;93446;93447	chr2:178535691;178535690;178535689	chr2:179400418;179400417;179400416
N2B	24577	73954;73955;73956	chr2:178535691;178535690;178535689	chr2:179400418;179400417;179400416
Novex-1	24702	74329;74330;74331	chr2:178535691;178535690;178535689	chr2:179400418;179400417;179400416
Novex-2	24769	74530;74531;74532	chr2:178535691;178535690;178535689	chr2:179400418;179400417;179400416
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-159
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1184
• 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
Y/D	rs774270109	-3.443	1.0	N	0.776	0.622	0.813587418085	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
Y/D	rs774270109	-3.443	1.0	N	0.776	0.622	0.813587418085	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
Y/D	rs774270109	-3.443	1.0	N	0.776	0.622	0.813587418085	gnomAD-4.0.0	3.09845E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.23808E-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
Y/A	0.9014	likely_pathogenic	0.8323	pathogenic	-2.758	Highly Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
Y/C	0.3918	ambiguous	0.226	benign	-1.983	Destabilizing	1.0	D	0.772	deleterious	N	0.508675791	None	None	N
Y/D	0.9369	likely_pathogenic	0.8852	pathogenic	-2.766	Highly Destabilizing	1.0	D	0.776	deleterious	N	0.50918277	None	None	N
Y/E	0.9745	likely_pathogenic	0.9457	pathogenic	-2.578	Highly Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
Y/F	0.2039	likely_benign	0.1716	benign	-1.08	Destabilizing	0.994	D	0.53	neutral	N	0.483169441	None	None	N
Y/G	0.8732	likely_pathogenic	0.8061	pathogenic	-3.179	Highly Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
Y/H	0.5665	likely_pathogenic	0.3925	ambiguous	-1.844	Destabilizing	0.401	N	0.363	neutral	N	0.474416672	None	None	N
Y/I	0.8692	likely_pathogenic	0.7648	pathogenic	-1.391	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
Y/K	0.9536	likely_pathogenic	0.8996	pathogenic	-2.162	Highly Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
Y/L	0.8124	likely_pathogenic	0.7279	pathogenic	-1.391	Destabilizing	0.987	D	0.621	neutral	None	None	None	None	N
Y/M	0.9189	likely_pathogenic	0.8633	pathogenic	-1.243	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
Y/N	0.7568	likely_pathogenic	0.6147	pathogenic	-2.882	Highly Destabilizing	1.0	D	0.709	prob.delet.	N	0.497572975	None	None	N
Y/P	0.9796	likely_pathogenic	0.9707	pathogenic	-1.857	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
Y/Q	0.9256	likely_pathogenic	0.8368	pathogenic	-2.612	Highly Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
Y/R	0.8729	likely_pathogenic	0.7609	pathogenic	-1.989	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
Y/S	0.6913	likely_pathogenic	0.5492	ambiguous	-3.315	Highly Destabilizing	1.0	D	0.677	prob.neutral	N	0.496812507	None	None	N
Y/T	0.8476	likely_pathogenic	0.7447	pathogenic	-2.998	Highly Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
Y/V	0.7646	likely_pathogenic	0.6627	pathogenic	-1.857	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
Y/W	0.6684	likely_pathogenic	0.6171	pathogenic	-0.515	Destabilizing	1.0	D	0.67	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.