TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14252	42979;42980;42981	chr2:178633605;178633604;178633603	chr2:179498332;179498331;179498330
N2AB	12611	38056;38057;38058	chr2:178633605;178633604;178633603	chr2:179498332;179498331;179498330
N2A	11684	35275;35276;35277	chr2:178633605;178633604;178633603	chr2:179498332;179498331;179498330
N2B	5187	15784;15785;15786	chr2:178633605;178633604;178633603	chr2:179498332;179498331;179498330
Novex-1	5312	16159;16160;16161	chr2:178633605;178633604;178633603	chr2:179498332;179498331;179498330
Novex-2	5379	16360;16361;16362	chr2:178633605;178633604;178633603	chr2:179498332;179498331;179498330
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-93
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1251
• Site annotation: disulfide
• 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
C/G	rs1372237054	-2.542	0.97	D	0.859	0.571	0.699194967022	gnomAD-2.1.1	4.04E-06	None	None	disulfide	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
C/G	rs1372237054	-2.542	0.97	D	0.859	0.571	0.699194967022	gnomAD-3.1.2	1.31E-05	None	None	disulfide	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
C/G	rs1372237054	-2.542	0.97	D	0.859	0.571	0.699194967022	gnomAD-4.0.0	5.57904E-06	None	None	disulfide	None	N	None	1.06812E-04	0	None	0	0	None	0	0	8.47746E-07	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
C/A	0.6123	likely_pathogenic	0.6506	pathogenic	-1.481	Destabilizing	0.717	D	0.666	neutral	None	None	disulfide	None	N
C/D	0.9962	likely_pathogenic	0.996	pathogenic	-1.712	Destabilizing	0.993	D	0.881	deleterious	None	None	disulfide	None	N
C/E	0.998	likely_pathogenic	0.9979	pathogenic	-1.463	Destabilizing	0.978	D	0.88	deleterious	None	None	disulfide	None	N
C/F	0.9365	likely_pathogenic	0.8903	pathogenic	-0.866	Destabilizing	0.89	D	0.846	deleterious	D	0.723625681	disulfide	None	N
C/G	0.575	likely_pathogenic	0.5327	ambiguous	-1.837	Destabilizing	0.97	D	0.859	deleterious	D	0.738562012	disulfide	None	N
C/H	0.996	likely_pathogenic	0.9952	pathogenic	-2.055	Highly Destabilizing	0.988	D	0.883	deleterious	None	None	disulfide	None	N
C/I	0.8084	likely_pathogenic	0.7537	pathogenic	-0.51	Destabilizing	0.956	D	0.815	deleterious	None	None	disulfide	None	N
C/K	0.9993	likely_pathogenic	0.9992	pathogenic	-1.18	Destabilizing	0.978	D	0.883	deleterious	None	None	disulfide	None	N
C/L	0.8632	likely_pathogenic	0.8068	pathogenic	-0.51	Destabilizing	0.754	D	0.742	deleterious	None	None	disulfide	None	N
C/M	0.9193	likely_pathogenic	0.9035	pathogenic	0.142	Stabilizing	0.998	D	0.783	deleterious	None	None	disulfide	None	N
C/N	0.9813	likely_pathogenic	0.9787	pathogenic	-1.89	Destabilizing	0.978	D	0.877	deleterious	None	None	disulfide	None	N
C/P	0.9981	likely_pathogenic	0.9979	pathogenic	-0.813	Destabilizing	0.993	D	0.868	deleterious	None	None	disulfide	None	N
C/Q	0.9962	likely_pathogenic	0.9962	pathogenic	-1.368	Destabilizing	0.978	D	0.873	deleterious	None	None	disulfide	None	N
C/R	0.9942	likely_pathogenic	0.9932	pathogenic	-1.619	Destabilizing	0.97	D	0.868	deleterious	D	0.792690354	disulfide	None	N
C/S	0.7425	likely_pathogenic	0.7554	pathogenic	-2.132	Highly Destabilizing	0.904	D	0.803	deleterious	D	0.723625681	disulfide	None	N
C/T	0.7175	likely_pathogenic	0.7473	pathogenic	-1.706	Destabilizing	0.978	D	0.807	deleterious	None	None	disulfide	None	N
C/V	0.5303	ambiguous	0.5166	ambiguous	-0.813	Destabilizing	0.86	D	0.78	deleterious	None	None	disulfide	None	N
C/W	0.9918	likely_pathogenic	0.9874	pathogenic	-1.349	Destabilizing	0.992	D	0.864	deleterious	D	0.792690354	disulfide	None	N
C/Y	0.9794	likely_pathogenic	0.9647	pathogenic	-1.111	Destabilizing	0.014	N	0.694	prob.neutral	D	0.791550777	disulfide	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.