TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19404	58435;58436;58437	chr2:178594183;178594182;178594181	chr2:179458910;179458909;179458908
N2AB	17763	53512;53513;53514	chr2:178594183;178594182;178594181	chr2:179458910;179458909;179458908
N2A	16836	50731;50732;50733	chr2:178594183;178594182;178594181	chr2:179458910;179458909;179458908
N2B	10339	31240;31241;31242	chr2:178594183;178594182;178594181	chr2:179458910;179458909;179458908
Novex-1	10464	31615;31616;31617	chr2:178594183;178594182;178594181	chr2:179458910;179458909;179458908
Novex-2	10531	31816;31817;31818	chr2:178594183;178594182;178594181	chr2:179458910;179458909;179458908
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-118
• Domain position: 14
• Structural Position: 28
• Q(SASA): 0.3324
• 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	0.959	N	0.556	0.316	0.541239005379	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-06	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	0.9562	likely_pathogenic	0.9208	pathogenic	-2.727	Highly Destabilizing	0.863	D	0.462	neutral	None	None	None	None	N
F/C	0.8149	likely_pathogenic	0.7474	pathogenic	-2.29	Highly Destabilizing	0.015	N	0.405	neutral	N	0.458806062	None	None	N
F/D	0.9973	likely_pathogenic	0.9949	pathogenic	-2.662	Highly Destabilizing	0.997	D	0.643	neutral	None	None	None	None	N
F/E	0.9968	likely_pathogenic	0.994	pathogenic	-2.48	Highly Destabilizing	0.997	D	0.646	neutral	None	None	None	None	N
F/G	0.988	likely_pathogenic	0.9768	pathogenic	-3.129	Highly Destabilizing	0.969	D	0.611	neutral	None	None	None	None	N
F/H	0.9826	likely_pathogenic	0.9729	pathogenic	-1.596	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
F/I	0.443	ambiguous	0.3856	ambiguous	-1.436	Destabilizing	0.959	D	0.518	neutral	N	0.442199027	None	None	N
F/K	0.9972	likely_pathogenic	0.9953	pathogenic	-2.495	Highly Destabilizing	0.997	D	0.642	neutral	None	None	None	None	N
F/L	0.9494	likely_pathogenic	0.9363	pathogenic	-1.436	Destabilizing	0.826	D	0.493	neutral	N	0.429499088	None	None	N
F/M	0.7996	likely_pathogenic	0.7485	pathogenic	-1.306	Destabilizing	0.997	D	0.543	neutral	None	None	None	None	N
F/N	0.9925	likely_pathogenic	0.9874	pathogenic	-2.893	Highly Destabilizing	0.997	D	0.655	neutral	None	None	None	None	N
F/P	0.9988	likely_pathogenic	0.9977	pathogenic	-1.874	Destabilizing	0.997	D	0.66	neutral	None	None	None	None	N
F/Q	0.994	likely_pathogenic	0.9892	pathogenic	-2.805	Highly Destabilizing	0.997	D	0.659	neutral	None	None	None	None	N
F/R	0.9933	likely_pathogenic	0.9887	pathogenic	-2.024	Highly Destabilizing	0.997	D	0.659	neutral	None	None	None	None	N
F/S	0.9735	likely_pathogenic	0.9472	pathogenic	-3.578	Highly Destabilizing	0.959	D	0.556	neutral	N	0.455589982	None	None	N
F/T	0.9615	likely_pathogenic	0.9302	pathogenic	-3.276	Highly Destabilizing	0.969	D	0.57	neutral	None	None	None	None	N
F/V	0.5221	ambiguous	0.4475	ambiguous	-1.874	Destabilizing	0.92	D	0.506	neutral	N	0.425629277	None	None	N
F/W	0.8548	likely_pathogenic	0.8281	pathogenic	-0.62	Destabilizing	0.999	D	0.548	neutral	None	None	None	None	N
F/Y	0.6314	likely_pathogenic	0.59	pathogenic	-1.013	Destabilizing	0.986	D	0.519	neutral	N	0.462337932	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.