TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6907	20944;20945;20946	chr2:178725485;178725484;178725483	chr2:179590212;179590211;179590210
N2AB	6590	19993;19994;19995	chr2:178725485;178725484;178725483	chr2:179590212;179590211;179590210
N2A	5663	17212;17213;17214	chr2:178725485;178725484;178725483	chr2:179590212;179590211;179590210
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-53
• Domain position: 54
• Structural Position: 131
• Q(SASA): 0.6816
• 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
E/Q	None	None	0.001	N	0.151	0.084	0.104622674875	gnomAD-4.0.0	1.59251E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02572E-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
E/A	0.1726	likely_benign	0.1725	benign	-0.032	Destabilizing	0.012	N	0.267	neutral	N	0.489686329	None	None	I
E/C	0.808	likely_pathogenic	0.8038	pathogenic	-0.298	Destabilizing	0.864	D	0.16	neutral	None	None	None	None	I
E/D	0.0695	likely_benign	0.0615	benign	-0.415	Destabilizing	None	N	0.115	neutral	N	0.430579311	None	None	I
E/F	0.8228	likely_pathogenic	0.8102	pathogenic	-0.102	Destabilizing	0.628	D	0.188	neutral	None	None	None	None	I
E/G	0.0785	likely_benign	0.0814	benign	-0.133	Destabilizing	None	N	0.165	neutral	N	0.469825558	None	None	I
E/H	0.3715	ambiguous	0.3625	ambiguous	0.551	Stabilizing	0.214	N	0.198	neutral	None	None	None	None	I
E/I	0.6725	likely_pathogenic	0.6751	pathogenic	0.173	Stabilizing	0.356	N	0.233	neutral	None	None	None	None	I
E/K	0.1271	likely_benign	0.1277	benign	0.32	Stabilizing	0.001	N	0.202	neutral	N	0.491398483	None	None	I
E/L	0.5503	ambiguous	0.5525	ambiguous	0.173	Stabilizing	0.072	N	0.299	neutral	None	None	None	None	I
E/M	0.623	likely_pathogenic	0.6237	pathogenic	-0.093	Destabilizing	0.356	N	0.171	neutral	None	None	None	None	I
E/N	0.1289	likely_benign	0.1159	benign	0.082	Stabilizing	None	N	0.119	neutral	None	None	None	None	I
E/P	0.4722	ambiguous	0.477	ambiguous	0.122	Stabilizing	0.136	N	0.293	neutral	None	None	None	None	I
E/Q	0.1295	likely_benign	0.1323	benign	0.085	Stabilizing	0.001	N	0.151	neutral	N	0.494612146	None	None	I
E/R	0.1996	likely_benign	0.2076	benign	0.569	Stabilizing	0.038	N	0.208	neutral	None	None	None	None	I
E/S	0.1504	likely_benign	0.1484	benign	-0.045	Destabilizing	0.003	N	0.212	neutral	None	None	None	None	I
E/T	0.3054	likely_benign	0.3105	benign	0.046	Stabilizing	0.038	N	0.281	neutral	None	None	None	None	I
E/V	0.4549	ambiguous	0.464	ambiguous	0.122	Stabilizing	0.055	N	0.309	neutral	N	0.479507588	None	None	I
E/W	0.8408	likely_pathogenic	0.8393	pathogenic	-0.071	Destabilizing	0.864	D	0.182	neutral	None	None	None	None	I
E/Y	0.5885	likely_pathogenic	0.5729	pathogenic	0.112	Stabilizing	0.356	N	0.193	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.