TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2965	9118;9119;9120	chr2:178769688;178769687;178769686	chr2:179634415;179634414;179634413
N2AB	2965	9118;9119;9120	chr2:178769688;178769687;178769686	chr2:179634415;179634414;179634413
N2A	2965	9118;9119;9120	chr2:178769688;178769687;178769686	chr2:179634415;179634414;179634413
N2B	2919	8980;8981;8982	chr2:178769688;178769687;178769686	chr2:179634415;179634414;179634413
Novex-1	2919	8980;8981;8982	chr2:178769688;178769687;178769686	chr2:179634415;179634414;179634413
Novex-2	2919	8980;8981;8982	chr2:178769688;178769687;178769686	chr2:179634415;179634414;179634413
Novex-3	2965	9118;9119;9120	chr2:178769688;178769687;178769686	chr2:179634415;179634414;179634413

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-19
• Domain position: 84
• Structural Position: 171
• Q(SASA): 0.2596
• 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/K	rs1221486073	None	0.002	D	0.318	0.277	0.397691132334	gnomAD-4.0.0	4.10926E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49855E-06	0	1.66152E-05

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	0.1073	likely_benign	0.1039	benign	-0.763	Destabilizing	0.201	N	0.536	neutral	D	0.601492066	None	None	N
T/C	0.4625	ambiguous	0.4739	ambiguous	-0.546	Destabilizing	0.982	D	0.723	prob.delet.	None	None	None	None	N
T/D	0.4745	ambiguous	0.4688	ambiguous	-0.003	Destabilizing	0.7	D	0.727	prob.delet.	None	None	None	None	N
T/E	0.253	likely_benign	0.2292	benign	-0.028	Destabilizing	0.25	N	0.651	neutral	None	None	None	None	N
T/F	0.2902	likely_benign	0.2784	benign	-0.972	Destabilizing	0.935	D	0.753	deleterious	None	None	None	None	N
T/G	0.4256	ambiguous	0.3965	ambiguous	-0.974	Destabilizing	0.399	N	0.666	neutral	None	None	None	None	N
T/H	0.17	likely_benign	0.154	benign	-1.258	Destabilizing	0.947	D	0.743	deleterious	None	None	None	None	N
T/I	0.1602	likely_benign	0.1566	benign	-0.303	Destabilizing	0.781	D	0.759	deleterious	N	0.516716452	None	None	N
T/K	0.0864	likely_benign	0.067	benign	-0.551	Destabilizing	0.002	N	0.318	neutral	D	0.541862009	None	None	N
T/L	0.1225	likely_benign	0.1131	benign	-0.303	Destabilizing	0.399	N	0.639	neutral	None	None	None	None	N
T/M	0.0897	likely_benign	0.0849	benign	-0.035	Destabilizing	0.982	D	0.715	prob.delet.	None	None	None	None	N
T/N	0.15	likely_benign	0.1488	benign	-0.443	Destabilizing	0.7	D	0.633	neutral	None	None	None	None	N
T/P	0.7673	likely_pathogenic	0.7387	pathogenic	-0.426	Destabilizing	0.781	D	0.759	deleterious	D	0.694240454	None	None	N
T/Q	0.1426	likely_benign	0.1147	benign	-0.685	Destabilizing	0.539	D	0.759	deleterious	None	None	None	None	N
T/R	0.0941	likely_benign	0.0667	benign	-0.29	Destabilizing	0.468	N	0.715	prob.delet.	D	0.523067941	None	None	N
T/S	0.1413	likely_benign	0.1486	benign	-0.759	Destabilizing	0.201	N	0.529	neutral	D	0.554523544	None	None	N
T/V	0.1503	likely_benign	0.1485	benign	-0.426	Destabilizing	0.399	N	0.561	neutral	None	None	None	None	N
T/W	0.5843	likely_pathogenic	0.5381	ambiguous	-0.859	Destabilizing	0.982	D	0.717	prob.delet.	None	None	None	None	N
T/Y	0.3055	likely_benign	0.3057	benign	-0.623	Destabilizing	0.826	D	0.751	deleterious	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.