TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20229	60910;60911;60912	chr2:178591040;178591039;178591038	chr2:179455767;179455766;179455765
N2AB	18588	55987;55988;55989	chr2:178591040;178591039;178591038	chr2:179455767;179455766;179455765
N2A	17661	53206;53207;53208	chr2:178591040;178591039;178591038	chr2:179455767;179455766;179455765
N2B	11164	33715;33716;33717	chr2:178591040;178591039;178591038	chr2:179455767;179455766;179455765
Novex-1	11289	34090;34091;34092	chr2:178591040;178591039;178591038	chr2:179455767;179455766;179455765
Novex-2	11356	34291;34292;34293	chr2:178591040;178591039;178591038	chr2:179455767;179455766;179455765
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-34
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.2896
• 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
T/A	rs747588848	None	0.055	N	0.439	0.187	0.20549828249	gnomAD-4.0.0	2.73735E-06	None	None	None	None	N	None	0	0	None	0	2.52169E-05	None	0	0	2.69885E-06	0	0
T/I	None	None	0.124	N	0.512	0.166	0.259761712551	gnomAD-4.0.0	1.59205E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85987E-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
T/A	0.1097	likely_benign	0.1274	benign	-0.861	Destabilizing	0.055	N	0.439	neutral	N	0.486132131	None	None	N
T/C	0.2532	likely_benign	0.2672	benign	-0.35	Destabilizing	0.968	D	0.647	neutral	None	None	None	None	N
T/D	0.5113	ambiguous	0.6175	pathogenic	-0.166	Destabilizing	0.726	D	0.627	neutral	None	None	None	None	N
T/E	0.3356	likely_benign	0.4333	ambiguous	-0.031	Destabilizing	0.726	D	0.585	neutral	None	None	None	None	N
T/F	0.3752	ambiguous	0.4691	ambiguous	-0.753	Destabilizing	0.396	N	0.695	prob.neutral	None	None	None	None	N
T/G	0.2383	likely_benign	0.2769	benign	-1.218	Destabilizing	0.567	D	0.635	neutral	None	None	None	None	N
T/H	0.3035	likely_benign	0.3683	ambiguous	-1.219	Destabilizing	0.968	D	0.697	prob.neutral	None	None	None	None	N
T/I	0.2408	likely_benign	0.3024	benign	0.044	Stabilizing	0.124	N	0.512	neutral	N	0.488841156	None	None	N
T/K	0.1888	likely_benign	0.2504	benign	-0.12	Destabilizing	0.497	N	0.586	neutral	N	0.486132131	None	None	N
T/L	0.0648	likely_benign	0.077	benign	0.044	Stabilizing	0.001	N	0.342	neutral	None	None	None	None	N
T/M	0.0766	likely_benign	0.0854	benign	-0.004	Destabilizing	0.026	N	0.393	neutral	None	None	None	None	N
T/N	0.1212	likely_benign	0.1381	benign	-0.527	Destabilizing	0.726	D	0.512	neutral	None	None	None	None	N
T/P	0.0839	likely_benign	0.1083	benign	-0.226	Destabilizing	0.859	D	0.633	neutral	N	0.498202317	None	None	N
T/Q	0.1917	likely_benign	0.2215	benign	-0.401	Destabilizing	0.567	D	0.647	neutral	None	None	None	None	N
T/R	0.1568	likely_benign	0.2058	benign	-0.19	Destabilizing	0.497	N	0.63	neutral	N	0.475394483	None	None	N
T/S	0.1611	likely_benign	0.1907	benign	-0.889	Destabilizing	0.22	N	0.422	neutral	N	0.486688336	None	None	N
T/V	0.1711	likely_benign	0.1964	benign	-0.226	Destabilizing	0.157	N	0.439	neutral	None	None	None	None	N
T/W	0.6451	likely_pathogenic	0.7468	pathogenic	-0.81	Destabilizing	0.968	D	0.696	prob.neutral	None	None	None	None	N
T/Y	0.3445	ambiguous	0.4228	ambiguous	-0.445	Destabilizing	0.726	D	0.709	prob.delet.	None	None	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.