TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31251	93976;93977;93978	chr2:178547875;178547874;178547873	chr2:179412602;179412601;179412600
N2AB	29610	89053;89054;89055	chr2:178547875;178547874;178547873	chr2:179412602;179412601;179412600
N2A	28683	86272;86273;86274	chr2:178547875;178547874;178547873	chr2:179412602;179412601;179412600
N2B	22186	66781;66782;66783	chr2:178547875;178547874;178547873	chr2:179412602;179412601;179412600
Novex-1	22311	67156;67157;67158	chr2:178547875;178547874;178547873	chr2:179412602;179412601;179412600
Novex-2	22378	67357;67358;67359	chr2:178547875;178547874;178547873	chr2:179412602;179412601;179412600
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-151
• Domain position: 34
• Structural Position: 50
• Q(SASA): 0.1486
• 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	0.835	0.435	0.520002024791	gnomAD-4.0.0	1.59112E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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	0.4339	ambiguous	0.4917	ambiguous	-2.187	Highly Destabilizing	0.998	D	0.593	neutral	None	None	None	None	N
L/C	0.6343	likely_pathogenic	0.6622	pathogenic	-1.338	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
L/D	0.9089	likely_pathogenic	0.9309	pathogenic	-1.847	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/E	0.6196	likely_pathogenic	0.667	pathogenic	-1.715	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
L/F	0.2392	likely_benign	0.2461	benign	-1.405	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
L/G	0.7906	likely_pathogenic	0.8318	pathogenic	-2.648	Highly Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
L/H	0.308	likely_benign	0.3313	benign	-1.985	Destabilizing	0.844	D	0.54	neutral	None	None	None	None	N
L/I	0.1557	likely_benign	0.1662	benign	-0.909	Destabilizing	1.0	D	0.527	neutral	None	None	None	None	N
L/K	0.2354	likely_benign	0.2497	benign	-1.457	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
L/M	0.1243	likely_benign	0.1354	benign	-0.715	Destabilizing	1.0	D	0.737	prob.delet.	N	0.496036298	None	None	N
L/N	0.6468	likely_pathogenic	0.698	pathogenic	-1.517	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
L/P	0.9292	likely_pathogenic	0.962	pathogenic	-1.31	Destabilizing	1.0	D	0.835	deleterious	N	0.458681082	None	None	N
L/Q	0.2102	likely_benign	0.2403	benign	-1.52	Destabilizing	0.999	D	0.815	deleterious	N	0.457920613	None	None	N
L/R	0.1982	likely_benign	0.2053	benign	-1.06	Destabilizing	0.999	D	0.801	deleterious	N	0.397485457	None	None	N
L/S	0.5915	likely_pathogenic	0.6472	pathogenic	-2.256	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
L/T	0.4143	ambiguous	0.4749	ambiguous	-1.991	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
L/V	0.1618	likely_benign	0.1776	benign	-1.31	Destabilizing	0.999	D	0.459	neutral	N	0.468945698	None	None	N
L/W	0.2731	likely_benign	0.3063	benign	-1.67	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
L/Y	0.4074	ambiguous	0.4113	ambiguous	-1.385	Destabilizing	0.999	D	0.761	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.