TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5339	16240;16241;16242	chr2:178733278;178733277;178733276	chr2:179598005;179598004;179598003
N2AB	5022	15289;15290;15291	chr2:178733278;178733277;178733276	chr2:179598005;179598004;179598003
N2A	4095	12508;12509;12510	chr2:178733278;178733277;178733276	chr2:179598005;179598004;179598003
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-36
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.541
• 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
V/L	rs2080875658	None	0.489	D	0.472	0.261	0.376216005999	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
V/A	0.1811	likely_benign	0.1612	benign	-0.316	Destabilizing	0.014	N	0.299	neutral	N	0.515799148	None	None	I
V/C	0.8493	likely_pathogenic	0.8278	pathogenic	-0.791	Destabilizing	0.994	D	0.561	neutral	None	None	None	None	I
V/D	0.704	likely_pathogenic	0.6494	pathogenic	-0.333	Destabilizing	0.978	D	0.663	neutral	None	None	None	None	I
V/E	0.5827	likely_pathogenic	0.5511	ambiguous	-0.456	Destabilizing	0.942	D	0.58	neutral	N	0.513435504	None	None	I
V/F	0.1626	likely_benign	0.146	benign	-0.73	Destabilizing	0.915	D	0.499	neutral	None	None	None	None	I
V/G	0.3915	ambiguous	0.3492	ambiguous	-0.362	Destabilizing	0.698	D	0.561	neutral	N	0.506496517	None	None	I
V/H	0.7898	likely_pathogenic	0.7656	pathogenic	0.016	Stabilizing	0.994	D	0.659	neutral	None	None	None	None	I
V/I	0.1103	likely_benign	0.1097	benign	-0.339	Destabilizing	0.86	D	0.441	neutral	None	None	None	None	I
V/K	0.8054	likely_pathogenic	0.7908	pathogenic	-0.323	Destabilizing	0.956	D	0.592	neutral	None	None	None	None	I
V/L	0.4813	ambiguous	0.4281	ambiguous	-0.339	Destabilizing	0.489	N	0.472	neutral	D	0.524477346	None	None	I
V/M	0.2626	likely_benign	0.2498	benign	-0.525	Destabilizing	0.99	D	0.483	neutral	N	0.509320901	None	None	I
V/N	0.5847	likely_pathogenic	0.5407	ambiguous	-0.133	Destabilizing	0.978	D	0.667	neutral	None	None	None	None	I
V/P	0.9625	likely_pathogenic	0.9542	pathogenic	-0.304	Destabilizing	0.978	D	0.635	neutral	None	None	None	None	I
V/Q	0.6973	likely_pathogenic	0.6566	pathogenic	-0.358	Destabilizing	0.978	D	0.642	neutral	None	None	None	None	I
V/R	0.726	likely_pathogenic	0.6917	pathogenic	0.128	Stabilizing	0.978	D	0.663	neutral	None	None	None	None	I
V/S	0.3735	ambiguous	0.3348	benign	-0.44	Destabilizing	0.754	D	0.533	neutral	None	None	None	None	I
V/T	0.3119	likely_benign	0.2939	benign	-0.473	Destabilizing	0.86	D	0.458	neutral	None	None	None	None	I
V/W	0.8688	likely_pathogenic	0.8559	pathogenic	-0.775	Destabilizing	0.998	D	0.69	prob.neutral	None	None	None	None	I
V/Y	0.612	likely_pathogenic	0.5742	pathogenic	-0.499	Destabilizing	0.16	N	0.401	neutral	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.