TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29426	88501;88502;88503	chr2:178556878;178556877;178556876	chr2:179421605;179421604;179421603
N2AB	27785	83578;83579;83580	chr2:178556878;178556877;178556876	chr2:179421605;179421604;179421603
N2A	26858	80797;80798;80799	chr2:178556878;178556877;178556876	chr2:179421605;179421604;179421603
N2B	20361	61306;61307;61308	chr2:178556878;178556877;178556876	chr2:179421605;179421604;179421603
Novex-1	20486	61681;61682;61683	chr2:178556878;178556877;178556876	chr2:179421605;179421604;179421603
Novex-2	20553	61882;61883;61884	chr2:178556878;178556877;178556876	chr2:179421605;179421604;179421603
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-102
• Domain position: 92
• Structural Position: 124
• Q(SASA): 0.9511
• 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/A	None	None	None	N	0.093	0.039	0.177238962908	gnomAD-4.0.0	5.474E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.19555E-06	0	0
V/G	None	None	0.104	N	0.415	0.113	0.292062946507	gnomAD-4.0.0	6.8425E-07	None	None	None	None	I	None	0	2.23624E-05	None	0	0	None	0	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
V/A	0.0873	likely_benign	0.0688	benign	-1.522	Destabilizing	None	N	0.093	neutral	N	0.435334556	None	None	I
V/C	0.6295	likely_pathogenic	0.5676	pathogenic	-1.072	Destabilizing	0.953	D	0.366	neutral	None	None	None	None	I
V/D	0.4896	ambiguous	0.3861	ambiguous	-1.714	Destabilizing	0.724	D	0.514	neutral	None	None	None	None	I
V/E	0.3923	ambiguous	0.3346	benign	-1.542	Destabilizing	0.361	N	0.433	neutral	N	0.481530993	None	None	I
V/F	0.21	likely_benign	0.1657	benign	-0.833	Destabilizing	0.842	D	0.451	neutral	None	None	None	None	I
V/G	0.2474	likely_benign	0.1905	benign	-2.009	Highly Destabilizing	0.104	N	0.415	neutral	N	0.467793691	None	None	I
V/H	0.633	likely_pathogenic	0.5531	ambiguous	-1.663	Destabilizing	0.984	D	0.464	neutral	None	None	None	None	I
V/I	0.0813	likely_benign	0.0772	benign	-0.208	Destabilizing	0.189	N	0.453	neutral	N	0.430888742	None	None	I
V/K	0.4827	ambiguous	0.4218	ambiguous	-1.315	Destabilizing	0.428	N	0.425	neutral	None	None	None	None	I
V/L	0.1556	likely_benign	0.1407	benign	-0.208	Destabilizing	0.104	N	0.435	neutral	N	0.437796071	None	None	I
V/M	0.1479	likely_benign	0.1316	benign	-0.252	Destabilizing	0.942	D	0.385	neutral	None	None	None	None	I
V/N	0.3824	ambiguous	0.2931	benign	-1.52	Destabilizing	0.724	D	0.508	neutral	None	None	None	None	I
V/P	0.5926	likely_pathogenic	0.4367	ambiguous	-0.614	Destabilizing	0.842	D	0.457	neutral	None	None	None	None	I
V/Q	0.4373	ambiguous	0.3714	ambiguous	-1.414	Destabilizing	0.842	D	0.481	neutral	None	None	None	None	I
V/R	0.4228	ambiguous	0.3593	ambiguous	-1.122	Destabilizing	0.724	D	0.526	neutral	None	None	None	None	I
V/S	0.1786	likely_benign	0.1353	benign	-2.131	Highly Destabilizing	0.01	N	0.293	neutral	None	None	None	None	I
V/T	0.1057	likely_benign	0.0885	benign	-1.814	Destabilizing	0.134	N	0.349	neutral	None	None	None	None	I
V/W	0.8128	likely_pathogenic	0.737	pathogenic	-1.277	Destabilizing	0.984	D	0.557	neutral	None	None	None	None	I
V/Y	0.6074	likely_pathogenic	0.5184	ambiguous	-0.843	Destabilizing	0.942	D	0.443	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.