TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31062	93409;93410;93411	chr2:178548442;178548441;178548440	chr2:179413169;179413168;179413167
N2AB	29421	88486;88487;88488	chr2:178548442;178548441;178548440	chr2:179413169;179413168;179413167
N2A	28494	85705;85706;85707	chr2:178548442;178548441;178548440	chr2:179413169;179413168;179413167
N2B	21997	66214;66215;66216	chr2:178548442;178548441;178548440	chr2:179413169;179413168;179413167
Novex-1	22122	66589;66590;66591	chr2:178548442;178548441;178548440	chr2:179413169;179413168;179413167
Novex-2	22189	66790;66791;66792	chr2:178548442;178548441;178548440	chr2:179413169;179413168;179413167
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-114
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.4938
• 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
S/G	None	None	0.973	N	0.415	0.135	0.212008924253	gnomAD-4.0.0	1.59113E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88267E-05	0	0	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	0.1142	likely_benign	0.1066	benign	-0.537	Destabilizing	0.398	N	0.278	neutral	None	None	None	None	N
S/C	0.2354	likely_benign	0.2121	benign	-0.446	Destabilizing	1.0	D	0.473	neutral	N	0.483640597	None	None	N
S/D	0.9247	likely_pathogenic	0.8636	pathogenic	0.275	Stabilizing	0.999	D	0.357	neutral	None	None	None	None	N
S/E	0.9465	likely_pathogenic	0.8993	pathogenic	0.23	Stabilizing	0.996	D	0.349	neutral	None	None	None	None	N
S/F	0.5592	ambiguous	0.4675	ambiguous	-0.89	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	N
S/G	0.1636	likely_benign	0.1411	benign	-0.711	Destabilizing	0.973	D	0.415	neutral	N	0.445157266	None	None	N
S/H	0.8013	likely_pathogenic	0.6961	pathogenic	-1.015	Destabilizing	1.0	D	0.475	neutral	None	None	None	None	N
S/I	0.4411	ambiguous	0.3752	ambiguous	-0.195	Destabilizing	0.998	D	0.587	neutral	N	0.518252302	None	None	N
S/K	0.9759	likely_pathogenic	0.9508	pathogenic	-0.546	Destabilizing	0.996	D	0.346	neutral	None	None	None	None	N
S/L	0.2357	likely_benign	0.19	benign	-0.195	Destabilizing	0.992	D	0.458	neutral	None	None	None	None	N
S/M	0.3912	ambiguous	0.3293	benign	-0.203	Destabilizing	1.0	D	0.463	neutral	None	None	None	None	N
S/N	0.4461	ambiguous	0.3303	benign	-0.367	Destabilizing	0.999	D	0.385	neutral	N	0.490372268	None	None	N
S/P	0.7626	likely_pathogenic	0.6573	pathogenic	-0.278	Destabilizing	0.999	D	0.451	neutral	None	None	None	None	N
S/Q	0.8637	likely_pathogenic	0.7787	pathogenic	-0.515	Destabilizing	1.0	D	0.395	neutral	None	None	None	None	N
S/R	0.9582	likely_pathogenic	0.9229	pathogenic	-0.345	Destabilizing	0.998	D	0.447	neutral	N	0.475288172	None	None	N
S/T	0.1207	likely_benign	0.107	benign	-0.455	Destabilizing	0.989	D	0.405	neutral	N	0.414317071	None	None	N
S/V	0.3828	ambiguous	0.3215	benign	-0.278	Destabilizing	0.992	D	0.445	neutral	None	None	None	None	N
S/W	0.7717	likely_pathogenic	0.6783	pathogenic	-0.895	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
S/Y	0.5655	likely_pathogenic	0.4518	ambiguous	-0.623	Destabilizing	1.0	D	0.591	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.