TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6071	18436;18437;18438	chr2:178730189;178730188;178730187	chr2:179594916;179594915;179594914
N2AB	5754	17485;17486;17487	chr2:178730189;178730188;178730187	chr2:179594916;179594915;179594914
N2A	4827	14704;14705;14706	chr2:178730189;178730188;178730187	chr2:179594916;179594915;179594914
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: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-44
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0976
• 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
L/R	None	None	0.928	D	0.884	0.735	0.863873001299	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
L/A	0.8667	likely_pathogenic	0.8724	pathogenic	-2.858	Highly Destabilizing	0.547	D	0.693	prob.neutral	None	None	None	None	N
L/C	0.7911	likely_pathogenic	0.7891	pathogenic	-2.073	Highly Destabilizing	0.985	D	0.784	deleterious	None	None	None	None	N
L/D	0.9803	likely_pathogenic	0.9791	pathogenic	-3.377	Highly Destabilizing	0.981	D	0.893	deleterious	None	None	None	None	N
L/E	0.9477	likely_pathogenic	0.9485	pathogenic	-3.111	Highly Destabilizing	0.945	D	0.89	deleterious	None	None	None	None	N
L/F	0.1676	likely_benign	0.1516	benign	-1.675	Destabilizing	0.864	D	0.763	deleterious	D	0.533656977	None	None	N
L/G	0.9547	likely_pathogenic	0.9542	pathogenic	-3.435	Highly Destabilizing	0.945	D	0.889	deleterious	None	None	None	None	N
L/H	0.7941	likely_pathogenic	0.7644	pathogenic	-2.874	Highly Destabilizing	0.993	D	0.865	deleterious	D	0.540960735	None	None	N
L/I	0.0795	likely_benign	0.0831	benign	-1.158	Destabilizing	0.024	N	0.353	neutral	N	0.423584341	None	None	N
L/K	0.9208	likely_pathogenic	0.9121	pathogenic	-2.336	Highly Destabilizing	0.945	D	0.879	deleterious	None	None	None	None	N
L/M	0.1923	likely_benign	0.1846	benign	-1.126	Destabilizing	0.894	D	0.701	prob.neutral	None	None	None	None	N
L/N	0.9088	likely_pathogenic	0.9074	pathogenic	-2.799	Highly Destabilizing	0.981	D	0.899	deleterious	None	None	None	None	N
L/P	0.9678	likely_pathogenic	0.9635	pathogenic	-1.71	Destabilizing	0.975	D	0.894	deleterious	D	0.52960443	None	None	N
L/Q	0.8357	likely_pathogenic	0.8232	pathogenic	-2.604	Highly Destabilizing	0.981	D	0.892	deleterious	None	None	None	None	N
L/R	0.8589	likely_pathogenic	0.8425	pathogenic	-2.043	Highly Destabilizing	0.928	D	0.884	deleterious	D	0.540960735	None	None	N
L/S	0.929	likely_pathogenic	0.9321	pathogenic	-3.466	Highly Destabilizing	0.894	D	0.885	deleterious	None	None	None	None	N
L/T	0.86	likely_pathogenic	0.8689	pathogenic	-3.054	Highly Destabilizing	0.894	D	0.809	deleterious	None	None	None	None	N
L/V	0.1538	likely_benign	0.1607	benign	-1.71	Destabilizing	0.006	N	0.339	neutral	N	0.486364346	None	None	N
L/W	0.5418	ambiguous	0.4809	ambiguous	-2.115	Highly Destabilizing	0.995	D	0.849	deleterious	None	None	None	None	N
L/Y	0.5717	likely_pathogenic	0.5347	ambiguous	-1.86	Destabilizing	0.945	D	0.8	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.