TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14948	45067;45068;45069	chr2:178622741;178622740;178622739	chr2:179487468;179487467;179487466
N2AB	13307	40144;40145;40146	chr2:178622741;178622740;178622739	chr2:179487468;179487467;179487466
N2A	12380	37363;37364;37365	chr2:178622741;178622740;178622739	chr2:179487468;179487467;179487466
N2B	5883	17872;17873;17874	chr2:178622741;178622740;178622739	chr2:179487468;179487467;179487466
Novex-1	6008	18247;18248;18249	chr2:178622741;178622740;178622739	chr2:179487468;179487467;179487466
Novex-2	6075	18448;18449;18450	chr2:178622741;178622740;178622739	chr2:179487468;179487467;179487466
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-101
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2299
• 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/P	None	None	1.0	N	0.912	0.552	0.546044812627	gnomAD-4.0.0	1.61472E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.89392E-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	0.9263	likely_pathogenic	0.917	pathogenic	-2.071	Highly Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
L/C	0.9638	likely_pathogenic	0.9573	pathogenic	-1.5	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/D	0.9988	likely_pathogenic	0.9987	pathogenic	-1.633	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
L/E	0.9925	likely_pathogenic	0.9913	pathogenic	-1.451	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/F	0.8654	likely_pathogenic	0.8383	pathogenic	-1.241	Destabilizing	1.0	D	0.719	prob.delet.	D	0.583579029	None	None	N
L/G	0.9921	likely_pathogenic	0.99	pathogenic	-2.575	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
L/H	0.991	likely_pathogenic	0.9892	pathogenic	-1.966	Destabilizing	1.0	D	0.893	deleterious	D	0.648195777	None	None	N
L/I	0.3309	likely_benign	0.3277	benign	-0.65	Destabilizing	0.999	D	0.513	neutral	N	0.45148626	None	None	N
L/K	0.9886	likely_pathogenic	0.9879	pathogenic	-1.175	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/M	0.4648	ambiguous	0.4405	ambiguous	-0.732	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
L/N	0.9934	likely_pathogenic	0.9922	pathogenic	-1.339	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/P	0.9495	likely_pathogenic	0.93	pathogenic	-1.1	Destabilizing	1.0	D	0.912	deleterious	N	0.431808006	None	None	N
L/Q	0.9763	likely_pathogenic	0.9733	pathogenic	-1.255	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
L/R	0.981	likely_pathogenic	0.9789	pathogenic	-0.99	Destabilizing	1.0	D	0.896	deleterious	D	0.683604551	None	None	N
L/S	0.9904	likely_pathogenic	0.9888	pathogenic	-2.155	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
L/T	0.9664	likely_pathogenic	0.9611	pathogenic	-1.824	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
L/V	0.3885	ambiguous	0.3737	ambiguous	-1.1	Destabilizing	0.999	D	0.49	neutral	D	0.582289623	None	None	N
L/W	0.99	likely_pathogenic	0.9871	pathogenic	-1.484	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/Y	0.9935	likely_pathogenic	0.9924	pathogenic	-1.18	Destabilizing	1.0	D	0.871	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.