TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5038	15337;15338;15339	chr2:178734812;178734811;178734810	chr2:179599539;179599538;179599537
N2AB	4721	14386;14387;14388	chr2:178734812;178734811;178734810	chr2:179599539;179599538;179599537
N2A	3794	11605;11606;11607	chr2:178734812;178734811;178734810	chr2:179599539;179599538;179599537
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-33
• Domain position: 58
• Structural Position: 137
• Q(SASA): 0.0847
• 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
I/T	rs949151920	None	None	N	0.351	0.162	0.533759884177	gnomAD-4.0.0	1.5913E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02407E-05
I/V	rs2081160150	None	None	N	0.127	0.107	0.233785782151	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.2389	likely_benign	0.24	benign	-2.564	Highly Destabilizing	0.007	N	0.499	neutral	None	None	None	None	N
I/C	0.5779	likely_pathogenic	0.6242	pathogenic	-1.608	Destabilizing	0.356	N	0.613	neutral	None	None	None	None	N
I/D	0.6674	likely_pathogenic	0.6292	pathogenic	-3.092	Highly Destabilizing	0.136	N	0.678	prob.neutral	None	None	None	None	N
I/E	0.5329	ambiguous	0.4772	ambiguous	-2.884	Highly Destabilizing	0.136	N	0.632	neutral	None	None	None	None	N
I/F	0.1202	likely_benign	0.1209	benign	-1.537	Destabilizing	0.072	N	0.579	neutral	None	None	None	None	N
I/G	0.5196	ambiguous	0.5276	ambiguous	-3.061	Highly Destabilizing	0.136	N	0.629	neutral	None	None	None	None	N
I/H	0.3877	ambiguous	0.3911	ambiguous	-2.658	Highly Destabilizing	0.864	D	0.635	neutral	None	None	None	None	N
I/K	0.3521	ambiguous	0.3227	benign	-1.905	Destabilizing	0.055	N	0.653	neutral	N	0.462835306	None	None	N
I/L	0.1075	likely_benign	0.1127	benign	-1.113	Destabilizing	0.002	N	0.357	neutral	N	0.464647879	None	None	N
I/M	0.0946	likely_benign	0.0949	benign	-0.934	Destabilizing	0.171	N	0.573	neutral	N	0.49465076	None	None	N
I/N	0.2246	likely_benign	0.2177	benign	-2.207	Highly Destabilizing	0.356	N	0.677	prob.neutral	None	None	None	None	N
I/P	0.9569	likely_pathogenic	0.9597	pathogenic	-1.582	Destabilizing	0.356	N	0.677	prob.neutral	None	None	None	None	N
I/Q	0.3765	ambiguous	0.3584	ambiguous	-2.082	Highly Destabilizing	0.628	D	0.649	neutral	None	None	None	None	N
I/R	0.2641	likely_benign	0.2473	benign	-1.619	Destabilizing	0.295	N	0.669	neutral	N	0.430537488	None	None	N
I/S	0.1932	likely_benign	0.1883	benign	-2.79	Highly Destabilizing	0.016	N	0.572	neutral	None	None	None	None	N
I/T	0.1532	likely_benign	0.1435	benign	-2.462	Highly Destabilizing	None	N	0.351	neutral	N	0.372224668	None	None	N
I/V	0.0548	likely_benign	0.0549	benign	-1.582	Destabilizing	None	N	0.127	neutral	N	0.351703795	None	None	N
I/W	0.7307	likely_pathogenic	0.7195	pathogenic	-2.049	Highly Destabilizing	0.864	D	0.656	neutral	None	None	None	None	N
I/Y	0.3962	ambiguous	0.3954	ambiguous	-1.786	Destabilizing	0.356	N	0.652	neutral	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.