TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8755	26488;26489;26490	chr2:178714511;178714510;178714509	chr2:179579238;179579237;179579236
N2AB	8438	25537;25538;25539	chr2:178714511;178714510;178714509	chr2:179579238;179579237;179579236
N2A	7511	22756;22757;22758	chr2:178714511;178714510;178714509	chr2:179579238;179579237;179579236
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: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-73
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.2354
• Predicted PPI site: I

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/R	None	None	0.99	D	0.819	0.761	0.89627696007	gnomAD-4.0.0	1.59232E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85969E-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
L/A	0.7775	likely_pathogenic	0.8546	pathogenic	-2.563	Highly Destabilizing	0.612	D	0.715	prob.delet.	None	None	None	None	I
L/C	0.7598	likely_pathogenic	0.8433	pathogenic	-1.847	Destabilizing	0.996	D	0.687	prob.neutral	None	None	None	None	I
L/D	0.9886	likely_pathogenic	0.9936	pathogenic	-3.183	Highly Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	I
L/E	0.9418	likely_pathogenic	0.9653	pathogenic	-2.879	Highly Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	I
L/F	0.1058	likely_benign	0.1231	benign	-1.529	Destabilizing	0.004	N	0.405	neutral	None	None	None	None	I
L/G	0.9205	likely_pathogenic	0.9532	pathogenic	-3.149	Highly Destabilizing	0.997	D	0.834	deleterious	None	None	None	None	I
L/H	0.785	likely_pathogenic	0.8604	pathogenic	-2.671	Highly Destabilizing	0.991	D	0.802	deleterious	None	None	None	None	I
L/I	0.1125	likely_benign	0.1389	benign	-0.815	Destabilizing	0.044	N	0.649	neutral	None	None	None	None	I
L/K	0.8945	likely_pathogenic	0.9346	pathogenic	-2.074	Highly Destabilizing	0.909	D	0.82	deleterious	None	None	None	None	I
L/M	0.1242	likely_benign	0.1405	benign	-0.883	Destabilizing	0.02	N	0.561	neutral	D	0.533912192	None	None	I
L/N	0.9485	likely_pathogenic	0.969	pathogenic	-2.69	Highly Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	I
L/P	0.9755	likely_pathogenic	0.9832	pathogenic	-1.386	Destabilizing	0.999	D	0.831	deleterious	D	0.628917537	None	None	I
L/Q	0.7447	likely_pathogenic	0.8317	pathogenic	-2.394	Highly Destabilizing	0.991	D	0.811	deleterious	D	0.628917537	None	None	I
L/R	0.8308	likely_pathogenic	0.8966	pathogenic	-2.077	Highly Destabilizing	0.99	D	0.819	deleterious	D	0.628917537	None	None	I
L/S	0.9003	likely_pathogenic	0.9475	pathogenic	-3.31	Highly Destabilizing	0.997	D	0.804	deleterious	None	None	None	None	I
L/T	0.8394	likely_pathogenic	0.9044	pathogenic	-2.836	Highly Destabilizing	0.768	D	0.747	deleterious	None	None	None	None	I
L/V	0.1845	likely_benign	0.2491	benign	-1.386	Destabilizing	0.044	N	0.67	neutral	D	0.570331682	None	None	I
L/W	0.3902	ambiguous	0.4818	ambiguous	-1.879	Destabilizing	0.997	D	0.781	deleterious	None	None	None	None	I
L/Y	0.5321	ambiguous	0.6084	pathogenic	-1.613	Destabilizing	0.205	N	0.744	deleterious	None	None	None	None	I

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.