TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2783	8572;8573;8574	chr2:178770445;178770444;178770443	chr2:179635172;179635171;179635170
N2AB	2783	8572;8573;8574	chr2:178770445;178770444;178770443	chr2:179635172;179635171;179635170
N2A	2783	8572;8573;8574	chr2:178770445;178770444;178770443	chr2:179635172;179635171;179635170
N2B	2737	8434;8435;8436	chr2:178770445;178770444;178770443	chr2:179635172;179635171;179635170
Novex-1	2737	8434;8435;8436	chr2:178770445;178770444;178770443	chr2:179635172;179635171;179635170
Novex-2	2737	8434;8435;8436	chr2:178770445;178770444;178770443	chr2:179635172;179635171;179635170
Novex-3	2783	8572;8573;8574	chr2:178770445;178770444;178770443	chr2:179635172;179635171;179635170

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-17
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.8382
• 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
R/S	rs374375627	-0.217	0.027	N	0.361	0.271	0.213573922156	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	5.45E-05	None	0	None	0	0	0
R/S	rs374375627	-0.217	0.027	N	0.361	0.271	0.213573922156	gnomAD-4.0.0	1.36815E-06	None	None	None	None	N	None	2.98686E-05	0	None	0	0	None	0	0	8.99292E-07	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
R/A	0.3676	ambiguous	0.5634	ambiguous	-0.095	Destabilizing	0.035	N	0.336	neutral	None	None	None	None	N
R/C	0.2923	likely_benign	0.3689	ambiguous	-0.461	Destabilizing	0.935	D	0.315	neutral	None	None	None	None	N
R/D	0.5667	likely_pathogenic	0.7495	pathogenic	-0.438	Destabilizing	0.149	N	0.406	neutral	None	None	None	None	N
R/E	0.3754	ambiguous	0.5638	ambiguous	-0.42	Destabilizing	0.035	N	0.305	neutral	None	None	None	None	N
R/F	0.5633	ambiguous	0.7465	pathogenic	-0.494	Destabilizing	0.791	D	0.339	neutral	None	None	None	None	N
R/G	0.2085	likely_benign	0.3588	ambiguous	-0.175	Destabilizing	0.117	N	0.39	neutral	N	0.505252455	None	None	N
R/H	0.1302	likely_benign	0.1653	benign	-0.67	Destabilizing	0.555	D	0.406	neutral	None	None	None	None	N
R/I	0.2736	likely_benign	0.4662	ambiguous	0.068	Stabilizing	0.555	D	0.362	neutral	None	None	None	None	N
R/K	0.0849	likely_benign	0.0972	benign	-0.421	Destabilizing	None	N	0.183	neutral	N	0.368940553	None	None	N
R/L	0.2564	likely_benign	0.4162	ambiguous	0.068	Stabilizing	0.149	N	0.39	neutral	None	None	None	None	N
R/M	0.2607	likely_benign	0.4472	ambiguous	-0.298	Destabilizing	0.741	D	0.375	neutral	D	0.535821858	None	None	N
R/N	0.4068	ambiguous	0.5958	pathogenic	-0.394	Destabilizing	0.149	N	0.361	neutral	None	None	None	None	N
R/P	0.4241	ambiguous	0.5805	pathogenic	0.028	Stabilizing	0.262	N	0.395	neutral	None	None	None	None	N
R/Q	0.1204	likely_benign	0.1474	benign	-0.376	Destabilizing	0.081	N	0.383	neutral	None	None	None	None	N
R/S	0.3709	ambiguous	0.5681	pathogenic	-0.481	Destabilizing	0.027	N	0.361	neutral	N	0.517898234	None	None	N
R/T	0.2428	likely_benign	0.4203	ambiguous	-0.387	Destabilizing	0.117	N	0.385	neutral	N	0.517773665	None	None	N
R/V	0.3779	ambiguous	0.5489	ambiguous	0.028	Stabilizing	0.149	N	0.413	neutral	None	None	None	None	N
R/W	0.2382	likely_benign	0.3644	ambiguous	-0.753	Destabilizing	0.915	D	0.319	neutral	D	0.535821858	None	None	N
R/Y	0.4291	ambiguous	0.5995	pathogenic	-0.383	Destabilizing	0.555	D	0.366	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.