TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8288	25087;25088;25089	chr2:178718144;178718143;178718142	chr2:179582871;179582870;179582869
N2AB	7971	24136;24137;24138	chr2:178718144;178718143;178718142	chr2:179582871;179582870;179582869
N2A	7044	21355;21356;21357	chr2:178718144;178718143;178718142	chr2:179582871;179582870;179582869
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-68
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.3627
• 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
D/G	None	None	None	N	0.127	0.237	0.183819452728	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
D/N	rs372538009	None	0.042	N	0.264	0.172	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/N	rs372538009	None	0.042	N	0.264	0.172	None	gnomAD-4.0.0	2.57995E-06	None	None	None	None	I	None	3.38432E-05	0	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
D/A	0.0836	likely_benign	0.0767	benign	0.013	Stabilizing	None	N	0.159	neutral	N	0.440301312	None	None	I
D/C	0.6504	likely_pathogenic	0.6373	pathogenic	-0.025	Destabilizing	0.393	N	0.384	neutral	None	None	None	None	I
D/E	0.1916	likely_benign	0.161	benign	-0.446	Destabilizing	0.011	N	0.241	neutral	N	0.446821852	None	None	I
D/F	0.5562	ambiguous	0.5262	ambiguous	0.767	Stabilizing	0.89	D	0.433	neutral	None	None	None	None	I
D/G	0.1491	likely_benign	0.1311	benign	-0.385	Destabilizing	None	N	0.127	neutral	N	0.462794169	None	None	I
D/H	0.2587	likely_benign	0.2624	benign	0.573	Stabilizing	0.874	D	0.295	neutral	N	0.48586303	None	None	I
D/I	0.3974	ambiguous	0.388	ambiguous	1.067	Stabilizing	0.362	N	0.415	neutral	None	None	None	None	I
D/K	0.3051	likely_benign	0.3006	benign	0.04	Stabilizing	0.318	N	0.346	neutral	None	None	None	None	I
D/L	0.3408	ambiguous	0.3327	benign	1.067	Stabilizing	0.19	N	0.337	neutral	None	None	None	None	I
D/M	0.5867	likely_pathogenic	0.5411	ambiguous	1.247	Stabilizing	0.751	D	0.389	neutral	None	None	None	None	I
D/N	0.108	likely_benign	0.1054	benign	-0.67	Destabilizing	0.042	N	0.264	neutral	N	0.482110649	None	None	I
D/P	0.9561	likely_pathogenic	0.9636	pathogenic	0.744	Stabilizing	0.043	N	0.322	neutral	None	None	None	None	I
D/Q	0.2746	likely_benign	0.2526	benign	-0.444	Destabilizing	0.462	N	0.304	neutral	None	None	None	None	I
D/R	0.2933	likely_benign	0.2936	benign	0.269	Stabilizing	0.531	D	0.404	neutral	None	None	None	None	I
D/S	0.0906	likely_benign	0.0805	benign	-0.881	Destabilizing	0.005	N	0.099	neutral	None	None	None	None	I
D/T	0.2269	likely_benign	0.2026	benign	-0.535	Destabilizing	None	N	0.123	neutral	None	None	None	None	I
D/V	0.2242	likely_benign	0.2221	benign	0.744	Stabilizing	0.03	N	0.348	neutral	N	0.470162859	None	None	I
D/W	0.8757	likely_pathogenic	0.8727	pathogenic	0.953	Stabilizing	0.989	D	0.389	neutral	None	None	None	None	I
D/Y	0.2113	likely_benign	0.2273	benign	1.041	Stabilizing	0.859	D	0.415	neutral	N	0.511990839	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.