TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5854	17785;17786;17787	chr2:178731105;178731104;178731103	chr2:179595832;179595831;179595830
N2AB	5537	16834;16835;16836	chr2:178731105;178731104;178731103	chr2:179595832;179595831;179595830
N2A	4610	14053;14054;14055	chr2:178731105;178731104;178731103	chr2:179595832;179595831;179595830
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-42
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.214
• 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
A/D	None	None	1.0	N	0.847	0.47	0.738729810274	gnomAD-4.0.0	1.36846E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15931E-05	1.65673E-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
A/C	0.6423	likely_pathogenic	0.5901	pathogenic	-0.558	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
A/D	0.851	likely_pathogenic	0.8725	pathogenic	-1.223	Destabilizing	1.0	D	0.847	deleterious	N	0.483833132	None	None	N
A/E	0.7508	likely_pathogenic	0.7478	pathogenic	-1.122	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
A/F	0.7453	likely_pathogenic	0.7077	pathogenic	-0.544	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
A/G	0.2176	likely_benign	0.2368	benign	-1.011	Destabilizing	0.999	D	0.617	neutral	N	0.483579643	None	None	N
A/H	0.8595	likely_pathogenic	0.8443	pathogenic	-1.203	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
A/I	0.5455	ambiguous	0.4348	ambiguous	0.238	Stabilizing	0.994	D	0.742	deleterious	None	None	None	None	N
A/K	0.847	likely_pathogenic	0.8282	pathogenic	-0.938	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
A/L	0.5147	ambiguous	0.4324	ambiguous	0.238	Stabilizing	0.994	D	0.693	prob.neutral	None	None	None	None	N
A/M	0.5221	ambiguous	0.4375	ambiguous	0.098	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
A/N	0.7391	likely_pathogenic	0.7233	pathogenic	-0.97	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
A/P	0.4895	ambiguous	0.4234	ambiguous	-0.014	Destabilizing	1.0	D	0.791	deleterious	D	0.527074934	None	None	N
A/Q	0.7301	likely_pathogenic	0.7055	pathogenic	-0.921	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
A/R	0.7672	likely_pathogenic	0.752	pathogenic	-0.841	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
A/S	0.1391	likely_benign	0.1443	benign	-1.349	Destabilizing	0.998	D	0.622	neutral	N	0.483326153	None	None	N
A/T	0.1377	likely_benign	0.1239	benign	-1.128	Destabilizing	0.996	D	0.695	prob.neutral	N	0.494135797	None	None	N
A/V	0.2346	likely_benign	0.1815	benign	-0.014	Destabilizing	0.884	D	0.424	neutral	N	0.416447725	None	None	N
A/W	0.9373	likely_pathogenic	0.9268	pathogenic	-1.118	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
A/Y	0.8302	likely_pathogenic	0.804	pathogenic	-0.546	Destabilizing	1.0	D	0.862	deleterious	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.