TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3233	9922;9923;9924	chr2:178766387;178766386;178766385	chr2:179631114;179631113;179631112
N2AB	3233	9922;9923;9924	chr2:178766387;178766386;178766385	chr2:179631114;179631113;179631112
N2A	3233	9922;9923;9924	chr2:178766387;178766386;178766385	chr2:179631114;179631113;179631112
N2B	3187	9784;9785;9786	chr2:178766387;178766386;178766385	chr2:179631114;179631113;179631112
Novex-1	3187	9784;9785;9786	chr2:178766387;178766386;178766385	chr2:179631114;179631113;179631112
Novex-2	3187	9784;9785;9786	chr2:178766387;178766386;178766385	chr2:179631114;179631113;179631112
Novex-3	3233	9922;9923;9924	chr2:178766387;178766386;178766385	chr2:179631114;179631113;179631112

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-22
• Domain position: 87
• Structural Position: 177
• Q(SASA): 0.1515
• 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
V/I	None	None	0.997	N	0.451	0.268	0.419713421852	gnomAD-4.0.0	1.37494E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80923E-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
V/A	0.9059	likely_pathogenic	0.9702	pathogenic	-1.864	Destabilizing	0.999	D	0.434	neutral	N	0.480350036	None	None	N
V/C	0.9736	likely_pathogenic	0.9877	pathogenic	-1.68	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
V/D	0.9973	likely_pathogenic	0.9991	pathogenic	-2.763	Highly Destabilizing	1.0	D	0.717	prob.delet.	N	0.482565157	None	None	N
V/E	0.9888	likely_pathogenic	0.996	pathogenic	-2.713	Highly Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
V/F	0.9016	likely_pathogenic	0.9817	pathogenic	-1.387	Destabilizing	1.0	D	0.724	prob.delet.	N	0.482342171	None	None	N
V/G	0.9466	likely_pathogenic	0.9795	pathogenic	-2.208	Highly Destabilizing	1.0	D	0.706	prob.neutral	N	0.482565157	None	None	N
V/H	0.9975	likely_pathogenic	0.9992	pathogenic	-1.689	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
V/I	0.1263	likely_benign	0.1724	benign	-0.976	Destabilizing	0.997	D	0.451	neutral	N	0.399428329	None	None	N
V/K	0.9906	likely_pathogenic	0.9961	pathogenic	-1.568	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
V/L	0.743	likely_pathogenic	0.9109	pathogenic	-0.976	Destabilizing	0.997	D	0.456	neutral	N	0.435439974	None	None	N
V/M	0.7849	likely_pathogenic	0.9498	pathogenic	-0.987	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
V/N	0.9918	likely_pathogenic	0.9967	pathogenic	-1.636	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
V/P	0.993	likely_pathogenic	0.9951	pathogenic	-1.243	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
V/Q	0.9874	likely_pathogenic	0.9963	pathogenic	-1.805	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
V/R	0.9814	likely_pathogenic	0.9912	pathogenic	-1.066	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
V/S	0.9706	likely_pathogenic	0.9888	pathogenic	-2.08	Highly Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
V/T	0.9162	likely_pathogenic	0.957	pathogenic	-1.929	Destabilizing	0.999	D	0.604	neutral	None	None	None	None	N
V/W	0.998	likely_pathogenic	0.9996	pathogenic	-1.664	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
V/Y	0.9938	likely_pathogenic	0.9984	pathogenic	-1.367	Destabilizing	1.0	D	0.722	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.