TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22207	66844;66845;66846	chr2:178581649;178581648;178581647	chr2:179446376;179446375;179446374
N2AB	20566	61921;61922;61923	chr2:178581649;178581648;178581647	chr2:179446376;179446375;179446374
N2A	19639	59140;59141;59142	chr2:178581649;178581648;178581647	chr2:179446376;179446375;179446374
N2B	13142	39649;39650;39651	chr2:178581649;178581648;178581647	chr2:179446376;179446375;179446374
Novex-1	13267	40024;40025;40026	chr2:178581649;178581648;178581647	chr2:179446376;179446375;179446374
Novex-2	13334	40225;40226;40227	chr2:178581649;178581648;178581647	chr2:179446376;179446375;179446374
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-49
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1068
• 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
N/K	rs2047770950	None	0.41	N	0.609	0.166	0.139678290688	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/K	rs2047770950	None	0.41	N	0.609	0.166	0.139678290688	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
N/A	0.8817	likely_pathogenic	0.8764	pathogenic	-1.046	Destabilizing	0.48	N	0.561	neutral	None	None	None	None	N
N/C	0.7046	likely_pathogenic	0.7031	pathogenic	-0.148	Destabilizing	0.98	D	0.769	deleterious	None	None	None	None	N
N/D	0.8174	likely_pathogenic	0.8291	pathogenic	-0.876	Destabilizing	0.41	N	0.541	neutral	N	0.520001741	None	None	N
N/E	0.9761	likely_pathogenic	0.9769	pathogenic	-0.674	Destabilizing	0.48	N	0.604	neutral	None	None	None	None	N
N/F	0.9732	likely_pathogenic	0.971	pathogenic	-0.585	Destabilizing	0.929	D	0.789	deleterious	None	None	None	None	N
N/G	0.8324	likely_pathogenic	0.8314	pathogenic	-1.47	Destabilizing	0.48	N	0.528	neutral	None	None	None	None	N
N/H	0.5776	likely_pathogenic	0.5668	pathogenic	-0.988	Destabilizing	0.908	D	0.749	deleterious	N	0.50740059	None	None	N
N/I	0.8614	likely_pathogenic	0.8448	pathogenic	0.08	Stabilizing	0.83	D	0.781	deleterious	D	0.52232997	None	None	N
N/K	0.9842	likely_pathogenic	0.985	pathogenic	-0.152	Destabilizing	0.41	N	0.609	neutral	N	0.517942871	None	None	N
N/L	0.862	likely_pathogenic	0.8527	pathogenic	0.08	Stabilizing	0.866	D	0.723	prob.delet.	None	None	None	None	N
N/M	0.9218	likely_pathogenic	0.9139	pathogenic	0.416	Stabilizing	0.993	D	0.755	deleterious	None	None	None	None	N
N/P	0.9259	likely_pathogenic	0.9373	pathogenic	-0.265	Destabilizing	0.866	D	0.741	deleterious	None	None	None	None	N
N/Q	0.946	likely_pathogenic	0.9453	pathogenic	-0.744	Destabilizing	0.866	D	0.752	deleterious	None	None	None	None	N
N/R	0.9681	likely_pathogenic	0.9711	pathogenic	-0.375	Destabilizing	0.866	D	0.725	prob.delet.	None	None	None	None	N
N/S	0.2429	likely_benign	0.2378	benign	-1.117	Destabilizing	0.004	N	0.373	neutral	N	0.508840598	None	None	N
N/T	0.4653	ambiguous	0.4299	ambiguous	-0.69	Destabilizing	0.41	N	0.583	neutral	N	0.43640171	None	None	N
N/V	0.8258	likely_pathogenic	0.8104	pathogenic	-0.265	Destabilizing	0.866	D	0.763	deleterious	None	None	None	None	N
N/W	0.9925	likely_pathogenic	0.9934	pathogenic	-0.34	Destabilizing	0.993	D	0.747	deleterious	None	None	None	None	N
N/Y	0.868	likely_pathogenic	0.8701	pathogenic	-0.079	Destabilizing	0.908	D	0.76	deleterious	D	0.522466043	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.