TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2936	9031;9032;9033	chr2:178769775;178769774;178769773	chr2:179634502;179634501;179634500
N2AB	2936	9031;9032;9033	chr2:178769775;178769774;178769773	chr2:179634502;179634501;179634500
N2A	2936	9031;9032;9033	chr2:178769775;178769774;178769773	chr2:179634502;179634501;179634500
N2B	2890	8893;8894;8895	chr2:178769775;178769774;178769773	chr2:179634502;179634501;179634500
Novex-1	2890	8893;8894;8895	chr2:178769775;178769774;178769773	chr2:179634502;179634501;179634500
Novex-2	2890	8893;8894;8895	chr2:178769775;178769774;178769773	chr2:179634502;179634501;179634500
Novex-3	2936	9031;9032;9033	chr2:178769775;178769774;178769773	chr2:179634502;179634501;179634500

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-19
• Domain position: 55
• Structural Position: 136
• Q(SASA): 0.1021
• 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
H/R	rs548456466	-1.46	1.0	N	0.692	0.641	0.40146981186	gnomAD-2.1.1	7.97E-06	None	None	None	None	N	None	0	0	None	0	5.44E-05	None	0	None	4.62E-05	0	0
H/R	rs548456466	-1.46	1.0	N	0.692	0.641	0.40146981186	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None

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
H/A	0.993	likely_pathogenic	0.9856	pathogenic	-2.032	Highly Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
H/C	0.8409	likely_pathogenic	0.7572	pathogenic	-1.172	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
H/D	0.9974	likely_pathogenic	0.9937	pathogenic	-1.993	Destabilizing	1.0	D	0.748	deleterious	D	0.648017231	None	None	N
H/E	0.9957	likely_pathogenic	0.9898	pathogenic	-1.78	Destabilizing	0.999	D	0.583	neutral	None	None	None	None	N
H/F	0.9381	likely_pathogenic	0.9023	pathogenic	0.032	Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
H/G	0.995	likely_pathogenic	0.9896	pathogenic	-2.463	Highly Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
H/I	0.9898	likely_pathogenic	0.9809	pathogenic	-0.737	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
H/K	0.988	likely_pathogenic	0.9791	pathogenic	-1.328	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
H/L	0.88	likely_pathogenic	0.7927	pathogenic	-0.737	Destabilizing	1.0	D	0.799	deleterious	D	0.583145418	None	None	N
H/M	0.987	likely_pathogenic	0.9777	pathogenic	-0.928	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
H/N	0.947	likely_pathogenic	0.8867	pathogenic	-2.099	Highly Destabilizing	0.999	D	0.597	neutral	D	0.591007689	None	None	N
H/P	0.9925	likely_pathogenic	0.9868	pathogenic	-1.162	Destabilizing	1.0	D	0.831	deleterious	D	0.672055556	None	None	N
H/Q	0.9658	likely_pathogenic	0.9328	pathogenic	-1.662	Destabilizing	1.0	D	0.719	prob.delet.	D	0.547162082	None	None	N
H/R	0.9329	likely_pathogenic	0.887	pathogenic	-1.515	Destabilizing	1.0	D	0.692	prob.neutral	N	0.508829541	None	None	N
H/S	0.9795	likely_pathogenic	0.9588	pathogenic	-2.241	Highly Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
H/T	0.9943	likely_pathogenic	0.9881	pathogenic	-1.906	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
H/V	0.9857	likely_pathogenic	0.9749	pathogenic	-1.162	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
H/W	0.9313	likely_pathogenic	0.9038	pathogenic	0.663	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
H/Y	0.7575	likely_pathogenic	0.6238	pathogenic	0.387	Stabilizing	0.999	D	0.613	neutral	N	0.496401503	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.