TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1542	4849;4850;4851	chr2:178777441;178777440;178777439	chr2:179642168;179642167;179642166
N2AB	1542	4849;4850;4851	chr2:178777441;178777440;178777439	chr2:179642168;179642167;179642166
N2A	1542	4849;4850;4851	chr2:178777441;178777440;178777439	chr2:179642168;179642167;179642166
N2B	1496	4711;4712;4713	chr2:178777441;178777440;178777439	chr2:179642168;179642167;179642166
Novex-1	1496	4711;4712;4713	chr2:178777441;178777440;178777439	chr2:179642168;179642167;179642166
Novex-2	1496	4711;4712;4713	chr2:178777441;178777440;178777439	chr2:179642168;179642167;179642166
Novex-3	1542	4849;4850;4851	chr2:178777441;178777440;178777439	chr2:179642168;179642167;179642166

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-6
• Domain position: 86
• Structural Position: 171
• Q(SASA): 0.4251
• 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
S/A	None	None	0.103	D	0.283	0.303	0.340273420219	gnomAD-4.0.0	1.59132E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85745E-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
S/A	0.0801	likely_benign	0.0862	benign	-0.389	Destabilizing	0.103	N	0.283	neutral	D	0.530081428	None	None	I
S/C	0.211	likely_benign	0.2227	benign	-0.399	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
S/D	0.5205	ambiguous	0.5839	pathogenic	0.294	Stabilizing	0.919	D	0.559	neutral	None	None	None	None	I
S/E	0.6393	likely_pathogenic	0.6907	pathogenic	0.24	Stabilizing	0.919	D	0.571	neutral	None	None	None	None	I
S/F	0.4517	ambiguous	0.4819	ambiguous	-0.83	Destabilizing	0.988	D	0.815	deleterious	None	None	None	None	I
S/G	0.1216	likely_benign	0.1376	benign	-0.558	Destabilizing	0.919	D	0.569	neutral	None	None	None	None	I
S/H	0.4265	ambiguous	0.4715	ambiguous	-1.053	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
S/I	0.4425	ambiguous	0.4652	ambiguous	-0.071	Destabilizing	0.976	D	0.79	deleterious	None	None	None	None	I
S/K	0.6371	likely_pathogenic	0.6868	pathogenic	-0.446	Destabilizing	0.919	D	0.571	neutral	None	None	None	None	I
S/L	0.2288	likely_benign	0.244	benign	-0.071	Destabilizing	0.811	D	0.727	prob.delet.	D	0.637474518	None	None	I
S/M	0.3722	ambiguous	0.3991	ambiguous	0.031	Stabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
S/N	0.1877	likely_benign	0.2168	benign	-0.32	Destabilizing	0.919	D	0.576	neutral	None	None	None	None	I
S/P	0.3004	likely_benign	0.3891	ambiguous	-0.145	Destabilizing	0.984	D	0.725	prob.delet.	D	0.577342597	None	None	I
S/Q	0.5407	ambiguous	0.5903	pathogenic	-0.484	Destabilizing	0.988	D	0.604	neutral	None	None	None	None	I
S/R	0.5556	ambiguous	0.6027	pathogenic	-0.331	Destabilizing	0.976	D	0.735	prob.delet.	None	None	None	None	I
S/T	0.0941	likely_benign	0.0993	benign	-0.386	Destabilizing	0.046	N	0.238	neutral	N	0.486906618	None	None	I
S/V	0.3441	ambiguous	0.3725	ambiguous	-0.145	Destabilizing	0.851	D	0.75	deleterious	None	None	None	None	I
S/W	0.6361	likely_pathogenic	0.6537	pathogenic	-0.834	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	I
S/Y	0.4088	ambiguous	0.422	ambiguous	-0.541	Destabilizing	0.996	D	0.815	deleterious	None	None	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.