TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14818	44677;44678;44679	chr2:178625369;178625368;178625367	chr2:179490096;179490095;179490094
N2AB	13177	39754;39755;39756	chr2:178625369;178625368;178625367	chr2:179490096;179490095;179490094
N2A	12250	36973;36974;36975	chr2:178625369;178625368;178625367	chr2:179490096;179490095;179490094
N2B	5753	17482;17483;17484	chr2:178625369;178625368;178625367	chr2:179490096;179490095;179490094
Novex-1	5878	17857;17858;17859	chr2:178625369;178625368;178625367	chr2:179490096;179490095;179490094
Novex-2	5945	18058;18059;18060	chr2:178625369;178625368;178625367	chr2:179490096;179490095;179490094
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-99
• Domain position: 54
• Structural Position: 136
• Q(SASA): 0.145
• 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/Y	None	None	0.999	N	0.614	0.443	0.28058544554	gnomAD-4.0.0	6.97275E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.68748E-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
H/A	0.8958	likely_pathogenic	0.8833	pathogenic	-1.745	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
H/C	0.4407	ambiguous	0.4183	ambiguous	-1.329	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
H/D	0.9536	likely_pathogenic	0.9658	pathogenic	-1.774	Destabilizing	1.0	D	0.749	deleterious	D	0.627265089	None	None	N
H/E	0.9551	likely_pathogenic	0.9628	pathogenic	-1.572	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
H/F	0.6863	likely_pathogenic	0.6576	pathogenic	0.089	Stabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
H/G	0.9509	likely_pathogenic	0.9549	pathogenic	-2.173	Highly Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
H/I	0.8518	likely_pathogenic	0.864	pathogenic	-0.48	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
H/K	0.8661	likely_pathogenic	0.9028	pathogenic	-1.203	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
H/L	0.5571	ambiguous	0.5648	pathogenic	-0.48	Destabilizing	1.0	D	0.806	deleterious	D	0.557286812	None	None	N
H/M	0.8963	likely_pathogenic	0.8978	pathogenic	-0.871	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
H/N	0.6041	likely_pathogenic	0.6508	pathogenic	-1.897	Destabilizing	0.999	D	0.595	neutral	D	0.587758515	None	None	N
H/P	0.9601	likely_pathogenic	0.9805	pathogenic	-0.892	Destabilizing	1.0	D	0.84	deleterious	D	0.565354002	None	None	N
H/Q	0.745	likely_pathogenic	0.75	pathogenic	-1.463	Destabilizing	1.0	D	0.723	prob.delet.	N	0.47035073	None	None	N
H/R	0.557	ambiguous	0.6329	pathogenic	-1.378	Destabilizing	1.0	D	0.693	prob.neutral	N	0.450927833	None	None	N
H/S	0.8369	likely_pathogenic	0.832	pathogenic	-2.083	Highly Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
H/T	0.9131	likely_pathogenic	0.9217	pathogenic	-1.755	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
H/V	0.8109	likely_pathogenic	0.8136	pathogenic	-0.892	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
H/W	0.7427	likely_pathogenic	0.7384	pathogenic	0.628	Stabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
H/Y	0.2547	likely_benign	0.2531	benign	0.479	Stabilizing	0.999	D	0.614	neutral	N	0.442829748	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.