TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8042	24349;24350;24351	chr2:178719266;178719265;178719264	chr2:179583993;179583992;179583991
N2AB	7725	23398;23399;23400	chr2:178719266;178719265;178719264	chr2:179583993;179583992;179583991
N2A	6798	20617;20618;20619	chr2:178719266;178719265;178719264	chr2:179583993;179583992;179583991
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: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-65
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0779
• 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/S	rs774349184	-3.319	0.925	D	0.835	0.653	0.886485767826	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
L/S	rs774349184	-3.319	0.925	D	0.835	0.653	0.886485767826	gnomAD-4.0.0	1.59125E-06	None	None	None	None	N	None	0	2.28645E-05	None	0	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
L/A	0.7459	likely_pathogenic	0.7964	pathogenic	-2.339	Highly Destabilizing	0.304	N	0.672	neutral	None	None	None	None	N
L/C	0.7988	likely_pathogenic	0.8231	pathogenic	-1.889	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
L/D	0.9957	likely_pathogenic	0.9969	pathogenic	-2.749	Highly Destabilizing	0.991	D	0.866	deleterious	None	None	None	None	N
L/E	0.9619	likely_pathogenic	0.9736	pathogenic	-2.443	Highly Destabilizing	0.983	D	0.849	deleterious	None	None	None	None	N
L/F	0.297	likely_benign	0.3238	benign	-1.464	Destabilizing	0.989	D	0.652	neutral	D	0.548361157	None	None	N
L/G	0.9375	likely_pathogenic	0.9551	pathogenic	-2.961	Highly Destabilizing	0.97	D	0.853	deleterious	None	None	None	None	N
L/H	0.881	likely_pathogenic	0.921	pathogenic	-2.741	Highly Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
L/I	0.1488	likely_benign	0.15	benign	-0.5	Destabilizing	0.985	D	0.713	prob.delet.	None	None	None	None	N
L/K	0.9109	likely_pathogenic	0.9465	pathogenic	-1.63	Destabilizing	0.983	D	0.835	deleterious	None	None	None	None	N
L/M	0.1589	likely_benign	0.1822	benign	-0.737	Destabilizing	0.998	D	0.672	neutral	D	0.53751183	None	None	N
L/N	0.9684	likely_pathogenic	0.9784	pathogenic	-2.23	Highly Destabilizing	0.996	D	0.872	deleterious	None	None	None	None	N
L/P	0.991	likely_pathogenic	0.9919	pathogenic	-1.099	Destabilizing	0.996	D	0.873	deleterious	None	None	None	None	N
L/Q	0.7726	likely_pathogenic	0.8451	pathogenic	-1.902	Destabilizing	0.746	D	0.749	deleterious	None	None	None	None	N
L/R	0.8113	likely_pathogenic	0.8756	pathogenic	-1.739	Destabilizing	0.991	D	0.845	deleterious	None	None	None	None	N
L/S	0.925	likely_pathogenic	0.947	pathogenic	-2.926	Highly Destabilizing	0.925	D	0.835	deleterious	D	0.584622573	None	None	N
L/T	0.8484	likely_pathogenic	0.8821	pathogenic	-2.439	Highly Destabilizing	0.97	D	0.808	deleterious	None	None	None	None	N
L/V	0.1535	likely_benign	0.1589	benign	-1.099	Destabilizing	0.961	D	0.713	prob.delet.	D	0.537258341	None	None	N
L/W	0.7121	likely_pathogenic	0.7698	pathogenic	-1.87	Destabilizing	0.29	N	0.735	prob.delet.	D	0.584622573	None	None	N
L/Y	0.774	likely_pathogenic	0.8247	pathogenic	-1.556	Destabilizing	0.991	D	0.788	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.