TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5358	16297;16298;16299	chr2:178733104;178733103;178733102	chr2:179597831;179597830;179597829
N2AB	5041	15346;15347;15348	chr2:178733104;178733103;178733102	chr2:179597831;179597830;179597829
N2A	4114	12565;12566;12567	chr2:178733104;178733103;178733102	chr2:179597831;179597830;179597829
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-37
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.384
• 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
F/L	None	None	None	N	0.107	0.062	0.18995819373	gnomAD-4.0.0	1.38517E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.08041E-07	1.19832E-05	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
F/A	0.3037	likely_benign	0.1868	benign	-1.372	Destabilizing	0.016	N	0.28	neutral	None	None	None	None	N
F/C	0.2323	likely_benign	0.1526	benign	-0.608	Destabilizing	0.828	D	0.327	neutral	N	0.458233712	None	None	N
F/D	0.7116	likely_pathogenic	0.5418	ambiguous	0.39	Stabilizing	0.072	N	0.385	neutral	None	None	None	None	N
F/E	0.7176	likely_pathogenic	0.5844	pathogenic	0.417	Stabilizing	0.072	N	0.396	neutral	None	None	None	None	N
F/G	0.6353	likely_pathogenic	0.4582	ambiguous	-1.62	Destabilizing	0.038	N	0.335	neutral	None	None	None	None	N
F/H	0.4008	ambiguous	0.3017	benign	0.042	Stabilizing	0.628	D	0.326	neutral	None	None	None	None	N
F/I	0.1206	likely_benign	0.0872	benign	-0.683	Destabilizing	0.029	N	0.211	neutral	N	0.411730631	None	None	N
F/K	0.7235	likely_pathogenic	0.6083	pathogenic	-0.476	Destabilizing	0.072	N	0.387	neutral	None	None	None	None	N
F/L	0.5194	ambiguous	0.3836	ambiguous	-0.683	Destabilizing	None	N	0.107	neutral	N	0.434183416	None	None	N
F/M	0.3065	likely_benign	0.2223	benign	-0.605	Destabilizing	0.12	N	0.358	neutral	None	None	None	None	N
F/N	0.4416	ambiguous	0.2859	benign	-0.502	Destabilizing	0.072	N	0.388	neutral	None	None	None	None	N
F/P	0.9848	likely_pathogenic	0.9638	pathogenic	-0.898	Destabilizing	0.356	N	0.413	neutral	None	None	None	None	N
F/Q	0.5572	ambiguous	0.4345	ambiguous	-0.527	Destabilizing	0.356	N	0.428	neutral	None	None	None	None	N
F/R	0.5579	ambiguous	0.4384	ambiguous	0.04	Stabilizing	0.214	N	0.414	neutral	None	None	None	None	N
F/S	0.2088	likely_benign	0.1213	benign	-1.243	Destabilizing	0.001	N	0.277	neutral	N	0.346871076	None	None	N
F/T	0.2631	likely_benign	0.1564	benign	-1.121	Destabilizing	None	N	0.219	neutral	None	None	None	None	N
F/V	0.1035	likely_benign	0.0772	benign	-0.898	Destabilizing	0.012	N	0.263	neutral	N	0.396547748	None	None	N
F/W	0.458	ambiguous	0.3666	ambiguous	-0.169	Destabilizing	0.864	D	0.366	neutral	None	None	None	None	N
F/Y	0.1298	likely_benign	0.1105	benign	-0.298	Destabilizing	0.106	N	0.312	neutral	N	0.411383914	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.