TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21036	63331;63332;63333	chr2:178588619;178588618;178588617	chr2:179453346;179453345;179453344
N2AB	19395	58408;58409;58410	chr2:178588619;178588618;178588617	chr2:179453346;179453345;179453344
N2A	18468	55627;55628;55629	chr2:178588619;178588618;178588617	chr2:179453346;179453345;179453344
N2B	11971	36136;36137;36138	chr2:178588619;178588618;178588617	chr2:179453346;179453345;179453344
Novex-1	12096	36511;36512;36513	chr2:178588619;178588618;178588617	chr2:179453346;179453345;179453344
Novex-2	12163	36712;36713;36714	chr2:178588619;178588618;178588617	chr2:179453346;179453345;179453344
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-40
• Domain position: 74
• Structural Position: 106
• Q(SASA): 0.1426
• 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
F/L	rs1031673060	None	0.999	N	0.637	0.509	0.515430650102	gnomAD-4.0.0	1.64234E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.92836E-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
F/A	0.9994	likely_pathogenic	0.9992	pathogenic	-2.875	Highly Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
F/C	0.9883	likely_pathogenic	0.986	pathogenic	-1.782	Destabilizing	1.0	D	0.796	deleterious	D	0.552239864	None	None	N
F/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.815	Highly Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
F/E	0.9999	likely_pathogenic	0.9998	pathogenic	-3.569	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
F/G	0.9992	likely_pathogenic	0.999	pathogenic	-3.342	Highly Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
F/H	0.9952	likely_pathogenic	0.9942	pathogenic	-2.317	Highly Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
F/I	0.9849	likely_pathogenic	0.9782	pathogenic	-1.32	Destabilizing	1.0	D	0.755	deleterious	N	0.490210736	None	None	N
F/K	0.9998	likely_pathogenic	0.9998	pathogenic	-2.494	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
F/L	0.9967	likely_pathogenic	0.9961	pathogenic	-1.32	Destabilizing	0.999	D	0.637	neutral	N	0.497074044	None	None	N
F/M	0.9909	likely_pathogenic	0.9879	pathogenic	-1.0	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
F/N	0.9989	likely_pathogenic	0.9985	pathogenic	-3.222	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
F/P	1.0	likely_pathogenic	1.0	pathogenic	-1.856	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
F/Q	0.9998	likely_pathogenic	0.9997	pathogenic	-3.024	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
F/R	0.9995	likely_pathogenic	0.9994	pathogenic	-2.266	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
F/S	0.9993	likely_pathogenic	0.999	pathogenic	-3.666	Highly Destabilizing	1.0	D	0.78	deleterious	D	0.552239864	None	None	N
F/T	0.9996	likely_pathogenic	0.9994	pathogenic	-3.293	Highly Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
F/V	0.9869	likely_pathogenic	0.9801	pathogenic	-1.856	Destabilizing	1.0	D	0.663	neutral	N	0.483445879	None	None	N
F/W	0.9125	likely_pathogenic	0.9038	pathogenic	-0.653	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
F/Y	0.3285	likely_benign	0.3224	benign	-1.091	Destabilizing	0.999	D	0.557	neutral	N	0.494026305	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.