TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6342	19249;19250;19251	chr2:178729014;178729013;178729012	chr2:179593741;179593740;179593739
N2AB	6025	18298;18299;18300	chr2:178729014;178729013;178729012	chr2:179593741;179593740;179593739
N2A	5098	15517;15518;15519	chr2:178729014;178729013;178729012	chr2:179593741;179593740;179593739
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-47
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.3871
• 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/S	None	None	0.997	N	0.727	0.564	0.829544206705	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.7066	likely_pathogenic	0.7269	pathogenic	-1.945	Destabilizing	0.992	D	0.707	prob.neutral	None	None	None	None	N
F/C	0.5509	ambiguous	0.584	pathogenic	-1.131	Destabilizing	1.0	D	0.791	deleterious	D	0.522168009	None	None	N
F/D	0.9143	likely_pathogenic	0.9199	pathogenic	-0.21	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
F/E	0.9244	likely_pathogenic	0.9224	pathogenic	-0.115	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
F/G	0.8842	likely_pathogenic	0.892	pathogenic	-2.276	Highly Destabilizing	0.269	N	0.517	neutral	None	None	None	None	N
F/H	0.7094	likely_pathogenic	0.7179	pathogenic	-0.561	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
F/I	0.3699	ambiguous	0.3847	ambiguous	-0.964	Destabilizing	0.999	D	0.713	prob.delet.	D	0.522245118	None	None	N
F/K	0.928	likely_pathogenic	0.9243	pathogenic	-1.047	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
F/L	0.8864	likely_pathogenic	0.8997	pathogenic	-0.964	Destabilizing	0.998	D	0.679	prob.neutral	N	0.511028046	None	None	N
F/M	0.612	likely_pathogenic	0.6168	pathogenic	-0.782	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
F/N	0.8127	likely_pathogenic	0.8026	pathogenic	-1.115	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
F/P	0.9902	likely_pathogenic	0.9933	pathogenic	-1.282	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
F/Q	0.887	likely_pathogenic	0.8782	pathogenic	-1.124	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
F/R	0.85	likely_pathogenic	0.8481	pathogenic	-0.488	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
F/S	0.542	ambiguous	0.5588	ambiguous	-1.987	Destabilizing	0.997	D	0.727	prob.delet.	N	0.521012967	None	None	N
F/T	0.6058	likely_pathogenic	0.6012	pathogenic	-1.799	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
F/V	0.3237	likely_benign	0.3308	benign	-1.282	Destabilizing	0.999	D	0.727	prob.delet.	D	0.524551917	None	None	N
F/W	0.6195	likely_pathogenic	0.6479	pathogenic	-0.092	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
F/Y	0.2328	likely_benign	0.2448	benign	-0.312	Destabilizing	0.998	D	0.667	neutral	N	0.449094153	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.