TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5169	15730;15731;15732	chr2:178733884;178733883;178733882	chr2:179598611;179598610;179598609
N2AB	4852	14779;14780;14781	chr2:178733884;178733883;178733882	chr2:179598611;179598610;179598609
N2A	3925	11998;11999;12000	chr2:178733884;178733883;178733882	chr2:179598611;179598610;179598609
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-35
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.4472
• 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/N	rs761475085	None	0.379	N	0.288	0.154	0.346085882481	gnomAD-4.0.0	1.6477E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.89459E-05	0	0	0	0
T/S	rs761475085	-0.496	0.007	N	0.11	0.149	0.168933306366	gnomAD-2.1.1	4.17E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.53E-05	None	0	0	0
T/S	rs761475085	-0.496	0.007	N	0.11	0.149	0.168933306366	gnomAD-4.0.0	1.6477E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.48854E-05	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	0.0644	likely_benign	0.0686	benign	-0.476	Destabilizing	0.099	N	0.17	neutral	N	0.495549489	None	None	N
T/C	0.3216	likely_benign	0.3734	ambiguous	-0.417	Destabilizing	0.992	D	0.325	neutral	None	None	None	None	N
T/D	0.3896	ambiguous	0.4398	ambiguous	0.428	Stabilizing	0.617	D	0.32	neutral	None	None	None	None	N
T/E	0.331	likely_benign	0.3665	ambiguous	0.428	Stabilizing	0.617	D	0.283	neutral	None	None	None	None	N
T/F	0.1566	likely_benign	0.1805	benign	-0.782	Destabilizing	0.85	D	0.385	neutral	None	None	None	None	N
T/G	0.1775	likely_benign	0.2138	benign	-0.681	Destabilizing	0.447	N	0.292	neutral	None	None	None	None	N
T/H	0.2082	likely_benign	0.2372	benign	-0.761	Destabilizing	0.977	D	0.347	neutral	None	None	None	None	N
T/I	0.0933	likely_benign	0.0905	benign	-0.037	Destabilizing	0.004	N	0.191	neutral	N	0.512622545	None	None	N
T/K	0.2234	likely_benign	0.2322	benign	-0.225	Destabilizing	0.447	N	0.327	neutral	None	None	None	None	N
T/L	0.0743	likely_benign	0.077	benign	-0.037	Destabilizing	0.103	N	0.285	neutral	None	None	None	None	N
T/M	0.0832	likely_benign	0.085	benign	-0.179	Destabilizing	0.85	D	0.331	neutral	None	None	None	None	N
T/N	0.1035	likely_benign	0.1163	benign	-0.258	Destabilizing	0.379	N	0.288	neutral	N	0.509608057	None	None	N
T/P	0.4325	ambiguous	0.456	ambiguous	-0.152	Destabilizing	0.896	D	0.369	neutral	D	0.553035678	None	None	N
T/Q	0.2079	likely_benign	0.2297	benign	-0.309	Destabilizing	0.85	D	0.371	neutral	None	None	None	None	N
T/R	0.1798	likely_benign	0.1838	benign	-0.043	Destabilizing	0.85	D	0.373	neutral	None	None	None	None	N
T/S	0.0815	likely_benign	0.0907	benign	-0.543	Destabilizing	0.007	N	0.11	neutral	N	0.422626058	None	None	N
T/V	0.0798	likely_benign	0.0804	benign	-0.152	Destabilizing	0.021	N	0.115	neutral	None	None	None	None	N
T/W	0.5225	ambiguous	0.5826	pathogenic	-0.816	Destabilizing	0.992	D	0.425	neutral	None	None	None	None	N
T/Y	0.1995	likely_benign	0.2454	benign	-0.497	Destabilizing	0.92	D	0.374	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.