TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3065	9418;9419;9420	chr2:178768126;178768125;178768124	chr2:179632853;179632852;179632851
N2AB	3065	9418;9419;9420	chr2:178768126;178768125;178768124	chr2:179632853;179632852;179632851
N2A	3065	9418;9419;9420	chr2:178768126;178768125;178768124	chr2:179632853;179632852;179632851
N2B	3019	9280;9281;9282	chr2:178768126;178768125;178768124	chr2:179632853;179632852;179632851
Novex-1	3019	9280;9281;9282	chr2:178768126;178768125;178768124	chr2:179632853;179632852;179632851
Novex-2	3019	9280;9281;9282	chr2:178768126;178768125;178768124	chr2:179632853;179632852;179632851
Novex-3	3065	9418;9419;9420	chr2:178768126;178768125;178768124	chr2:179632853;179632852;179632851

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-21
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.6026
• Predicted PPI site: I

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
K/Q	None	None	1.0	N	0.771	0.506	0.339793275041	gnomAD-4.0.0	3.18139E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71311E-06	0	0
K/T	rs747328944	-0.279	1.0	N	0.755	0.613	0.600719443016	gnomAD-2.1.1	1.99E-05	None	None	None	None	I	None	0	1.44709E-04	None	0	0	None	0	None	0	0	0
K/T	rs747328944	-0.279	1.0	N	0.755	0.613	0.600719443016	gnomAD-4.0.0	7.95342E-06	None	None	None	None	I	None	0	1.14338E-04	None	0	0	None	0	0	0	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
K/A	0.8673	likely_pathogenic	0.845	pathogenic	-0.114	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	I
K/C	0.9665	likely_pathogenic	0.9601	pathogenic	-0.424	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
K/D	0.9334	likely_pathogenic	0.9301	pathogenic	0.003	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
K/E	0.6627	likely_pathogenic	0.6156	pathogenic	0.057	Stabilizing	0.999	D	0.633	neutral	N	0.5081668	None	None	I
K/F	0.9888	likely_pathogenic	0.9889	pathogenic	-0.124	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
K/G	0.8854	likely_pathogenic	0.8635	pathogenic	-0.368	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
K/H	0.7087	likely_pathogenic	0.7023	pathogenic	-0.548	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
K/I	0.9353	likely_pathogenic	0.9299	pathogenic	0.491	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
K/L	0.8883	likely_pathogenic	0.8851	pathogenic	0.491	Stabilizing	1.0	D	0.639	neutral	None	None	None	None	I
K/M	0.8473	likely_pathogenic	0.8288	pathogenic	0.054	Stabilizing	1.0	D	0.724	prob.delet.	D	0.640324919	None	None	I
K/N	0.8854	likely_pathogenic	0.8772	pathogenic	-0.091	Destabilizing	1.0	D	0.791	deleterious	D	0.538681203	None	None	I
K/P	0.9521	likely_pathogenic	0.9586	pathogenic	0.318	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
K/Q	0.4369	ambiguous	0.3964	ambiguous	-0.16	Destabilizing	1.0	D	0.771	deleterious	N	0.502495203	None	None	I
K/R	0.1229	likely_benign	0.1258	benign	-0.188	Destabilizing	0.999	D	0.593	neutral	N	0.513619685	None	None	I
K/S	0.8664	likely_pathogenic	0.8429	pathogenic	-0.565	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	I
K/T	0.6656	likely_pathogenic	0.6196	pathogenic	-0.342	Destabilizing	1.0	D	0.755	deleterious	N	0.517143702	None	None	I
K/V	0.8902	likely_pathogenic	0.8821	pathogenic	0.318	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
K/W	0.9746	likely_pathogenic	0.9719	pathogenic	-0.141	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
K/Y	0.9671	likely_pathogenic	0.9671	pathogenic	0.189	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I

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.