TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14408	43447;43448;43449	chr2:178632784;178632783;178632782	chr2:179497511;179497510;179497509
N2AB	12767	38524;38525;38526	chr2:178632784;178632783;178632782	chr2:179497511;179497510;179497509
N2A	11840	35743;35744;35745	chr2:178632784;178632783;178632782	chr2:179497511;179497510;179497509
N2B	5343	16252;16253;16254	chr2:178632784;178632783;178632782	chr2:179497511;179497510;179497509
Novex-1	5468	16627;16628;16629	chr2:178632784;178632783;178632782	chr2:179497511;179497510;179497509
Novex-2	5535	16828;16829;16830	chr2:178632784;178632783;178632782	chr2:179497511;179497510;179497509
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-95
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.11
• 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
L/I	rs767777694	-0.59	0.122	D	0.229	0.386	0.397691132334	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	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
L/A	0.7654	likely_pathogenic	0.7674	pathogenic	-1.941	Destabilizing	0.97	D	0.495	neutral	None	None	None	None	N
L/C	0.8607	likely_pathogenic	0.8561	pathogenic	-1.104	Destabilizing	1.0	D	0.527	neutral	None	None	None	None	N
L/D	0.9868	likely_pathogenic	0.9866	pathogenic	-1.457	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	N
L/E	0.9332	likely_pathogenic	0.9377	pathogenic	-1.33	Destabilizing	0.999	D	0.582	neutral	None	None	None	None	N
L/F	0.5951	likely_pathogenic	0.5945	pathogenic	-1.106	Destabilizing	0.994	D	0.529	neutral	D	0.589504257	None	None	N
L/G	0.9581	likely_pathogenic	0.9545	pathogenic	-2.394	Highly Destabilizing	0.999	D	0.581	neutral	None	None	None	None	N
L/H	0.8924	likely_pathogenic	0.8965	pathogenic	-1.697	Destabilizing	1.0	D	0.595	neutral	D	0.589631778	None	None	N
L/I	0.1573	likely_benign	0.1485	benign	-0.7	Destabilizing	0.122	N	0.229	neutral	D	0.532382164	None	None	N
L/K	0.9211	likely_pathogenic	0.9207	pathogenic	-1.333	Destabilizing	0.999	D	0.537	neutral	None	None	None	None	N
L/M	0.2887	likely_benign	0.2773	benign	-0.563	Destabilizing	0.996	D	0.547	neutral	None	None	None	None	N
L/N	0.9161	likely_pathogenic	0.9198	pathogenic	-1.351	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
L/P	0.8116	likely_pathogenic	0.7681	pathogenic	-1.087	Destabilizing	0.998	D	0.592	neutral	D	0.54491417	None	None	N
L/Q	0.8369	likely_pathogenic	0.8368	pathogenic	-1.345	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	N
L/R	0.8651	likely_pathogenic	0.8641	pathogenic	-0.952	Destabilizing	0.998	D	0.544	neutral	D	0.589504257	None	None	N
L/S	0.878	likely_pathogenic	0.8808	pathogenic	-2.073	Highly Destabilizing	0.996	D	0.509	neutral	None	None	None	None	N
L/T	0.7435	likely_pathogenic	0.741	pathogenic	-1.813	Destabilizing	0.97	D	0.467	neutral	None	None	None	None	N
L/V	0.1664	likely_benign	0.1603	benign	-1.087	Destabilizing	0.248	N	0.258	neutral	D	0.548248356	None	None	N
L/W	0.876	likely_pathogenic	0.874	pathogenic	-1.349	Destabilizing	1.0	D	0.582	neutral	None	None	None	None	N
L/Y	0.9126	likely_pathogenic	0.9176	pathogenic	-1.063	Destabilizing	0.999	D	0.514	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.