TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28778	86557;86558;86559	chr2:178559800;178559799;178559798	chr2:179424527;179424526;179424525
N2AB	27137	81634;81635;81636	chr2:178559800;178559799;178559798	chr2:179424527;179424526;179424525
N2A	26210	78853;78854;78855	chr2:178559800;178559799;178559798	chr2:179424527;179424526;179424525
N2B	19713	59362;59363;59364	chr2:178559800;178559799;178559798	chr2:179424527;179424526;179424525
Novex-1	19838	59737;59738;59739	chr2:178559800;178559799;178559798	chr2:179424527;179424526;179424525
Novex-2	19905	59938;59939;59940	chr2:178559800;178559799;178559798	chr2:179424527;179424526;179424525
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-144
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.123
• Predicted PPI site: I

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/V	None	None	0.805	N	0.735	0.355	0.53832913131	gnomAD-4.0.0	1.37279E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80095E-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	0.9711	likely_pathogenic	0.958	pathogenic	-2.701	Highly Destabilizing	0.845	D	0.707	prob.neutral	None	None	None	None	I
F/C	0.7162	likely_pathogenic	0.6536	pathogenic	-1.537	Destabilizing	0.999	D	0.775	deleterious	N	0.509495031	None	None	I
F/D	0.9991	likely_pathogenic	0.9987	pathogenic	-2.126	Highly Destabilizing	0.975	D	0.819	deleterious	None	None	None	None	I
F/E	0.9985	likely_pathogenic	0.9979	pathogenic	-1.998	Destabilizing	0.975	D	0.817	deleterious	None	None	None	None	I
F/G	0.9917	likely_pathogenic	0.9885	pathogenic	-3.086	Highly Destabilizing	0.975	D	0.805	deleterious	None	None	None	None	I
F/H	0.9626	likely_pathogenic	0.9513	pathogenic	-1.368	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	I
F/I	0.5395	ambiguous	0.4591	ambiguous	-1.497	Destabilizing	0.892	D	0.697	prob.neutral	N	0.42024854	None	None	I
F/K	0.9968	likely_pathogenic	0.9959	pathogenic	-1.75	Destabilizing	0.975	D	0.817	deleterious	None	None	None	None	I
F/L	0.9621	likely_pathogenic	0.9479	pathogenic	-1.497	Destabilizing	0.805	D	0.642	neutral	N	0.511873408	None	None	I
F/M	0.865	likely_pathogenic	0.8243	pathogenic	-1.136	Destabilizing	0.996	D	0.717	prob.delet.	None	None	None	None	I
F/N	0.9935	likely_pathogenic	0.9911	pathogenic	-1.904	Destabilizing	0.975	D	0.823	deleterious	None	None	None	None	I
F/P	0.9994	likely_pathogenic	0.999	pathogenic	-1.9	Destabilizing	0.987	D	0.819	deleterious	None	None	None	None	I
F/Q	0.9933	likely_pathogenic	0.9908	pathogenic	-1.984	Destabilizing	0.987	D	0.823	deleterious	None	None	None	None	I
F/R	0.9913	likely_pathogenic	0.9886	pathogenic	-1.047	Destabilizing	0.975	D	0.824	deleterious	None	None	None	None	I
F/S	0.9671	likely_pathogenic	0.9527	pathogenic	-2.661	Highly Destabilizing	0.805	D	0.756	deleterious	N	0.486110857	None	None	I
F/T	0.977	likely_pathogenic	0.9674	pathogenic	-2.436	Highly Destabilizing	0.033	N	0.512	neutral	None	None	None	None	I
F/V	0.5425	ambiguous	0.4735	ambiguous	-1.9	Destabilizing	0.805	D	0.735	prob.delet.	N	0.422203049	None	None	I
F/W	0.8177	likely_pathogenic	0.7847	pathogenic	-0.505	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
F/Y	0.3277	likely_benign	0.307	benign	-0.799	Destabilizing	0.981	D	0.631	neutral	N	0.502216562	None	None	I

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.