TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9662	29209;29210;29211	chr2:178707583;178707582;178707581	chr2:179572310;179572309;179572308
N2AB	9345	28258;28259;28260	chr2:178707583;178707582;178707581	chr2:179572310;179572309;179572308
N2A	8418	25477;25478;25479	chr2:178707583;178707582;178707581	chr2:179572310;179572309;179572308
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: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-82
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.059
• 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/R	None	None	1.0	None	0.903	0.856	0.883469295186	gnomAD-4.0.0	1.59122E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	2.85801E-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
C/A	0.9209	likely_pathogenic	0.8958	pathogenic	-1.389	Destabilizing	0.998	D	0.727	prob.delet.	None	None	disulfide	None	N
C/D	0.9998	likely_pathogenic	0.9997	pathogenic	-1.423	Destabilizing	1.0	D	0.879	deleterious	None	None	disulfide	None	N
C/E	0.9998	likely_pathogenic	0.9997	pathogenic	-1.175	Destabilizing	1.0	D	0.899	deleterious	None	None	disulfide	None	N
C/F	0.9204	likely_pathogenic	0.8721	pathogenic	-0.749	Destabilizing	1.0	D	0.889	deleterious	None	None	disulfide	None	N
C/G	0.8816	likely_pathogenic	0.816	pathogenic	-1.751	Destabilizing	1.0	D	0.875	deleterious	None	None	disulfide	None	N
C/H	0.9991	likely_pathogenic	0.9987	pathogenic	-1.942	Destabilizing	1.0	D	0.897	deleterious	None	None	disulfide	None	N
C/I	0.8844	likely_pathogenic	0.8892	pathogenic	-0.4	Destabilizing	1.0	D	0.813	deleterious	None	None	disulfide	None	N
C/K	0.9998	likely_pathogenic	0.9998	pathogenic	-0.879	Destabilizing	1.0	D	0.878	deleterious	None	None	disulfide	None	N
C/L	0.8036	likely_pathogenic	0.7987	pathogenic	-0.4	Destabilizing	0.999	D	0.771	deleterious	None	None	disulfide	None	N
C/M	0.9644	likely_pathogenic	0.9609	pathogenic	0.38	Stabilizing	1.0	D	0.833	deleterious	None	None	disulfide	None	N
C/N	0.9985	likely_pathogenic	0.998	pathogenic	-1.573	Destabilizing	1.0	D	0.899	deleterious	None	None	disulfide	None	N
C/P	0.9991	likely_pathogenic	0.9987	pathogenic	-0.708	Destabilizing	1.0	D	0.899	deleterious	None	None	disulfide	None	N
C/Q	0.9992	likely_pathogenic	0.9988	pathogenic	-1.056	Destabilizing	1.0	D	0.908	deleterious	None	None	disulfide	None	N
C/R	0.9975	likely_pathogenic	0.9966	pathogenic	-1.371	Destabilizing	1.0	D	0.903	deleterious	None	None	disulfide	None	N
C/S	0.9761	likely_pathogenic	0.9629	pathogenic	-1.831	Destabilizing	1.0	D	0.804	deleterious	None	None	disulfide	None	N
C/T	0.9831	likely_pathogenic	0.9775	pathogenic	-1.401	Destabilizing	1.0	D	0.816	deleterious	None	None	disulfide	None	N
C/V	0.8018	likely_pathogenic	0.7985	pathogenic	-0.708	Destabilizing	0.999	D	0.794	deleterious	None	None	disulfide	None	N
C/W	0.9957	likely_pathogenic	0.9929	pathogenic	-1.194	Destabilizing	1.0	D	0.867	deleterious	None	None	disulfide	None	N
C/Y	0.9893	likely_pathogenic	0.9837	pathogenic	-0.961	Destabilizing	1.0	D	0.901	deleterious	None	None	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.