TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8432	25519;25520;25521	chr2:178717580;178717579;178717578	chr2:179582307;179582306;179582305
N2AB	8115	24568;24569;24570	chr2:178717580;178717579;178717578	chr2:179582307;179582306;179582305
N2A	7188	21787;21788;21789	chr2:178717580;178717579;178717578	chr2:179582307;179582306;179582305
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-69
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0761
• 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/Y	None	None	1.0	D	0.901	0.602	0.782265642558	gnomAD-4.0.0	6.84526E-07	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	8.99713E-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	0.9316	likely_pathogenic	0.9338	pathogenic	-1.579	Destabilizing	1.0	D	0.721	prob.delet.	None	None	disulfide	None	N
C/D	0.9997	likely_pathogenic	0.9996	pathogenic	-1.104	Destabilizing	1.0	D	0.881	deleterious	None	None	disulfide	None	N
C/E	0.9997	likely_pathogenic	0.9997	pathogenic	-0.874	Destabilizing	1.0	D	0.902	deleterious	None	None	disulfide	None	N
C/F	0.8528	likely_pathogenic	0.8604	pathogenic	-1.176	Destabilizing	1.0	D	0.889	deleterious	D	0.534404509	disulfide	None	N
C/G	0.8795	likely_pathogenic	0.8867	pathogenic	-1.926	Destabilizing	1.0	D	0.873	deleterious	D	0.547281751	disulfide	None	N
C/H	0.9983	likely_pathogenic	0.998	pathogenic	-2.208	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	disulfide	None	N
C/I	0.8666	likely_pathogenic	0.876	pathogenic	-0.645	Destabilizing	1.0	D	0.805	deleterious	None	None	disulfide	None	N
C/K	0.9998	likely_pathogenic	0.9997	pathogenic	-0.585	Destabilizing	1.0	D	0.88	deleterious	None	None	disulfide	None	N
C/L	0.807	likely_pathogenic	0.8076	pathogenic	-0.645	Destabilizing	1.0	D	0.765	deleterious	None	None	disulfide	None	N
C/M	0.9647	likely_pathogenic	0.9693	pathogenic	-0.072	Destabilizing	1.0	D	0.833	deleterious	None	None	disulfide	None	N
C/N	0.9981	likely_pathogenic	0.998	pathogenic	-1.163	Destabilizing	1.0	D	0.901	deleterious	None	None	disulfide	None	N
C/P	0.9992	likely_pathogenic	0.9992	pathogenic	-0.934	Destabilizing	1.0	D	0.901	deleterious	None	None	disulfide	None	N
C/Q	0.9991	likely_pathogenic	0.9989	pathogenic	-0.726	Destabilizing	1.0	D	0.909	deleterious	None	None	disulfide	None	N
C/R	0.9964	likely_pathogenic	0.9956	pathogenic	-1.121	Destabilizing	1.0	D	0.905	deleterious	D	0.547281751	disulfide	None	N
C/S	0.9784	likely_pathogenic	0.9798	pathogenic	-1.476	Destabilizing	1.0	D	0.797	deleterious	D	0.547281751	disulfide	None	N
C/T	0.9818	likely_pathogenic	0.9835	pathogenic	-1.049	Destabilizing	1.0	D	0.809	deleterious	None	None	disulfide	None	N
C/V	0.7725	likely_pathogenic	0.803	pathogenic	-0.934	Destabilizing	1.0	D	0.787	deleterious	None	None	disulfide	None	N
C/W	0.9942	likely_pathogenic	0.9941	pathogenic	-1.491	Destabilizing	1.0	D	0.863	deleterious	D	0.547281751	disulfide	None	N
C/Y	0.978	likely_pathogenic	0.9786	pathogenic	-1.261	Destabilizing	1.0	D	0.901	deleterious	D	0.547281751	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.