TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9058	27397;27398;27399	chr2:178712853;178712852;178712851	chr2:179577580;179577579;179577578
N2AB	8741	26446;26447;26448	chr2:178712853;178712852;178712851	chr2:179577580;179577579;179577578
N2A	7814	23665;23666;23667	chr2:178712853;178712852;178712851	chr2:179577580;179577579;179577578
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-76
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.4356
• 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
E/G	None	None	0.999	N	0.647	0.589	0.672538118423	gnomAD-4.0.0	6.84235E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99481E-07	0	0
E/Q	rs2154296273	None	0.916	N	0.287	0.239	0.3691244813	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
E/A	0.1599	likely_benign	0.1633	benign	-0.667	Destabilizing	0.992	D	0.634	neutral	N	0.498823515	None	None	N
E/C	0.8604	likely_pathogenic	0.8725	pathogenic	-0.343	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/D	0.3403	ambiguous	0.3541	ambiguous	-0.438	Destabilizing	0.992	D	0.487	neutral	N	0.49327688	None	None	N
E/F	0.7289	likely_pathogenic	0.7515	pathogenic	-0.111	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/G	0.2668	likely_benign	0.282	benign	-0.93	Destabilizing	0.999	D	0.647	neutral	N	0.520183454	None	None	N
E/H	0.481	ambiguous	0.5095	ambiguous	0.173	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/I	0.2694	likely_benign	0.277	benign	0.024	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/K	0.0936	likely_benign	0.0992	benign	0.182	Stabilizing	0.984	D	0.573	neutral	N	0.494010895	None	None	N
E/L	0.3194	likely_benign	0.3237	benign	0.024	Stabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	N
E/M	0.3651	ambiguous	0.3769	ambiguous	0.097	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/N	0.4072	ambiguous	0.4294	ambiguous	-0.481	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
E/P	0.3657	ambiguous	0.3918	ambiguous	-0.187	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/Q	0.1121	likely_benign	0.1172	benign	-0.382	Destabilizing	0.916	D	0.287	neutral	N	0.491657492	None	None	N
E/R	0.1796	likely_benign	0.1955	benign	0.54	Stabilizing	0.998	D	0.684	prob.neutral	None	None	None	None	N
E/S	0.2774	likely_benign	0.296	benign	-0.639	Destabilizing	0.994	D	0.639	neutral	None	None	None	None	N
E/T	0.2668	likely_benign	0.2783	benign	-0.404	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
E/V	0.1663	likely_benign	0.1708	benign	-0.187	Destabilizing	0.999	D	0.731	prob.delet.	N	0.487822831	None	None	N
E/W	0.9139	likely_pathogenic	0.9258	pathogenic	0.213	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/Y	0.6564	likely_pathogenic	0.6819	pathogenic	0.177	Stabilizing	1.0	D	0.733	prob.delet.	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.