TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15148	45667;45668;45669	chr2:178621276;178621275;178621274	chr2:179486003;179486002;179486001
N2AB	13507	40744;40745;40746	chr2:178621276;178621275;178621274	chr2:179486003;179486002;179486001
N2A	12580	37963;37964;37965	chr2:178621276;178621275;178621274	chr2:179486003;179486002;179486001
N2B	6083	18472;18473;18474	chr2:178621276;178621275;178621274	chr2:179486003;179486002;179486001
Novex-1	6208	18847;18848;18849	chr2:178621276;178621275;178621274	chr2:179486003;179486002;179486001
Novex-2	6275	19048;19049;19050	chr2:178621276;178621275;178621274	chr2:179486003;179486002;179486001
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-103
• Domain position: 29
• Structural Position: 44
• Q(SASA): 0.3385
• 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/I	None	None	0.012	N	0.167	0.224	0.29132392195	gnomAD-4.0.0	1.59449E-06	None	None	None	None	N	None	0	2.29421E-05	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
F/A	0.6826	likely_pathogenic	0.6314	pathogenic	-1.988	Destabilizing	0.688	D	0.423	neutral	None	None	None	None	N
F/C	0.5925	likely_pathogenic	0.4701	ambiguous	-0.924	Destabilizing	0.997	D	0.529	neutral	N	0.502028615	None	None	N
F/D	0.8974	likely_pathogenic	0.8422	pathogenic	-0.302	Destabilizing	0.991	D	0.584	neutral	None	None	None	None	N
F/E	0.8999	likely_pathogenic	0.8421	pathogenic	-0.226	Destabilizing	0.974	D	0.595	neutral	None	None	None	None	N
F/G	0.8995	likely_pathogenic	0.8547	pathogenic	-2.306	Highly Destabilizing	0.915	D	0.597	neutral	None	None	None	None	N
F/H	0.7052	likely_pathogenic	0.6429	pathogenic	-0.519	Destabilizing	0.949	D	0.523	neutral	None	None	None	None	N
F/I	0.2713	likely_benign	0.2094	benign	-1.049	Destabilizing	0.012	N	0.167	neutral	N	0.448589577	None	None	N
F/K	0.9382	likely_pathogenic	0.9066	pathogenic	-0.949	Destabilizing	0.974	D	0.599	neutral	None	None	None	None	N
F/L	0.8766	likely_pathogenic	0.8168	pathogenic	-1.049	Destabilizing	0.005	N	0.113	neutral	N	0.454036621	None	None	N
F/M	0.6053	likely_pathogenic	0.5238	ambiguous	-0.783	Destabilizing	0.949	D	0.481	neutral	None	None	None	None	N
F/N	0.7563	likely_pathogenic	0.6904	pathogenic	-0.954	Destabilizing	0.991	D	0.585	neutral	None	None	None	None	N
F/P	0.9882	likely_pathogenic	0.98	pathogenic	-1.353	Destabilizing	0.991	D	0.587	neutral	None	None	None	None	N
F/Q	0.8568	likely_pathogenic	0.8121	pathogenic	-1.02	Destabilizing	0.991	D	0.59	neutral	None	None	None	None	N
F/R	0.8993	likely_pathogenic	0.8612	pathogenic	-0.328	Destabilizing	0.974	D	0.587	neutral	None	None	None	None	N
F/S	0.5459	ambiguous	0.4989	ambiguous	-1.795	Destabilizing	0.891	D	0.532	neutral	N	0.465506486	None	None	N
F/T	0.6502	likely_pathogenic	0.5637	ambiguous	-1.63	Destabilizing	0.842	D	0.528	neutral	None	None	None	None	N
F/V	0.2707	likely_benign	0.2188	benign	-1.353	Destabilizing	0.454	N	0.387	neutral	N	0.410521107	None	None	N
F/W	0.7617	likely_pathogenic	0.7089	pathogenic	-0.184	Destabilizing	0.974	D	0.479	neutral	None	None	None	None	N
F/Y	0.2148	likely_benign	0.194	benign	-0.395	Destabilizing	0.005	N	0.116	neutral	N	0.426398598	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.