TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13708	41347;41348;41349	chr2:178636605;178636604;178636603	chr2:179501332;179501331;179501330
N2AB	12067	36424;36425;36426	chr2:178636605;178636604;178636603	chr2:179501332;179501331;179501330
N2A	11140	33643;33644;33645	chr2:178636605;178636604;178636603	chr2:179501332;179501331;179501330
N2B	4643	14152;14153;14154	chr2:178636605;178636604;178636603	chr2:179501332;179501331;179501330
Novex-1	4768	14527;14528;14529	chr2:178636605;178636604;178636603	chr2:179501332;179501331;179501330
Novex-2	4835	14728;14729;14730	chr2:178636605;178636604;178636603	chr2:179501332;179501331;179501330
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-87
• Domain position: 25
• Structural Position: 33
• Q(SASA): 0.1202
• 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/W	rs794729424	None	0.999	D	0.877	0.444	0.73502437085	gnomAD-4.0.0	1.3687E-06	None	None	disulfide	None	N	None	0	0	None	3.8279E-05	0	None	0	0	0	0	1.65728E-05
C/Y	None	None	0.995	D	0.875	0.495	0.77324528785	gnomAD-4.0.0	1.59205E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02645E-05

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	0.9397	likely_pathogenic	0.947	pathogenic	-1.725	Destabilizing	0.702	D	0.649	neutral	None	None	disulfide	None	N
C/D	0.9995	likely_pathogenic	0.9997	pathogenic	-1.827	Destabilizing	0.996	D	0.9	deleterious	None	None	disulfide	None	N
C/E	0.9998	likely_pathogenic	0.9999	pathogenic	-1.603	Destabilizing	0.988	D	0.903	deleterious	None	None	disulfide	None	N
C/F	0.9712	likely_pathogenic	0.9822	pathogenic	-1.071	Destabilizing	0.984	D	0.879	deleterious	D	0.763130383	disulfide	None	N
C/G	0.8991	likely_pathogenic	0.9279	pathogenic	-2.046	Highly Destabilizing	0.984	D	0.861	deleterious	D	0.678728884	disulfide	None	N
C/H	0.9991	likely_pathogenic	0.9995	pathogenic	-2.263	Highly Destabilizing	0.999	D	0.899	deleterious	None	None	disulfide	None	N
C/I	0.9612	likely_pathogenic	0.9524	pathogenic	-0.854	Destabilizing	0.851	D	0.736	prob.delet.	None	None	disulfide	None	N
C/K	0.9999	likely_pathogenic	0.9999	pathogenic	-1.553	Destabilizing	0.988	D	0.903	deleterious	None	None	disulfide	None	N
C/L	0.961	likely_pathogenic	0.9649	pathogenic	-0.854	Destabilizing	0.702	D	0.727	prob.delet.	None	None	disulfide	None	N
C/M	0.9763	likely_pathogenic	0.9793	pathogenic	-0.374	Destabilizing	0.988	D	0.801	deleterious	None	None	disulfide	None	N
C/N	0.9964	likely_pathogenic	0.9976	pathogenic	-2.055	Highly Destabilizing	0.996	D	0.896	deleterious	None	None	disulfide	None	N
C/P	0.9998	likely_pathogenic	0.9999	pathogenic	-1.125	Destabilizing	0.996	D	0.899	deleterious	None	None	disulfide	None	N
C/Q	0.9995	likely_pathogenic	0.9997	pathogenic	-1.595	Destabilizing	0.996	D	0.91	deleterious	None	None	disulfide	None	N
C/R	0.9992	likely_pathogenic	0.9994	pathogenic	-1.878	Destabilizing	0.984	D	0.898	deleterious	D	0.764247308	disulfide	None	N
C/S	0.9693	likely_pathogenic	0.9783	pathogenic	-2.345	Highly Destabilizing	0.946	D	0.787	deleterious	D	0.690796738	disulfide	None	N
C/T	0.9671	likely_pathogenic	0.9714	pathogenic	-1.965	Destabilizing	0.919	D	0.765	deleterious	None	None	disulfide	None	N
C/V	0.8531	likely_pathogenic	0.8168	pathogenic	-1.125	Destabilizing	0.034	N	0.621	neutral	None	None	disulfide	None	N
C/W	0.9986	likely_pathogenic	0.9993	pathogenic	-1.543	Destabilizing	0.999	D	0.877	deleterious	D	0.764247308	disulfide	None	N
C/Y	0.9942	likely_pathogenic	0.9967	pathogenic	-1.334	Destabilizing	0.995	D	0.875	deleterious	D	0.763130383	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.