TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2637	8134;8135;8136	chr2:178771418;178771417;178771416	chr2:179636145;179636144;179636143
N2AB	2637	8134;8135;8136	chr2:178771418;178771417;178771416	chr2:179636145;179636144;179636143
N2A	2637	8134;8135;8136	chr2:178771418;178771417;178771416	chr2:179636145;179636144;179636143
N2B	2591	7996;7997;7998	chr2:178771418;178771417;178771416	chr2:179636145;179636144;179636143
Novex-1	2591	7996;7997;7998	chr2:178771418;178771417;178771416	chr2:179636145;179636144;179636143
Novex-2	2591	7996;7997;7998	chr2:178771418;178771417;178771416	chr2:179636145;179636144;179636143
Novex-3	2637	8134;8135;8136	chr2:178771418;178771417;178771416	chr2:179636145;179636144;179636143

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-16
• Domain position: 17
• Structural Position: 28
• Q(SASA): 0.1424
• 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/V	None	None	1.0	N	0.615	0.424	0.305086939656	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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
A/C	0.7691	likely_pathogenic	0.7773	pathogenic	-0.82	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
A/D	0.9625	likely_pathogenic	0.9437	pathogenic	-1.49	Destabilizing	1.0	D	0.863	deleterious	N	0.498141573	None	None	N
A/E	0.9459	likely_pathogenic	0.9204	pathogenic	-1.356	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
A/F	0.907	likely_pathogenic	0.8937	pathogenic	-0.598	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
A/G	0.3613	ambiguous	0.3547	ambiguous	-1.281	Destabilizing	1.0	D	0.563	neutral	N	0.460795797	None	None	N
A/H	0.9811	likely_pathogenic	0.9731	pathogenic	-1.62	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
A/I	0.5165	ambiguous	0.5278	ambiguous	0.263	Stabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
A/K	0.9851	likely_pathogenic	0.976	pathogenic	-1.085	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
A/L	0.5926	likely_pathogenic	0.5842	pathogenic	0.263	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
A/M	0.6098	likely_pathogenic	0.6034	pathogenic	0.118	Stabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
A/N	0.9324	likely_pathogenic	0.9081	pathogenic	-1.144	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
A/P	0.9868	likely_pathogenic	0.9733	pathogenic	-0.061	Destabilizing	1.0	D	0.878	deleterious	N	0.498141573	None	None	N
A/Q	0.9524	likely_pathogenic	0.9338	pathogenic	-1.041	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
A/R	0.9716	likely_pathogenic	0.9577	pathogenic	-1.067	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
A/S	0.2726	likely_benign	0.2725	benign	-1.607	Destabilizing	1.0	D	0.585	neutral	N	0.326423869	None	None	N
A/T	0.2304	likely_benign	0.2355	benign	-1.343	Destabilizing	1.0	D	0.718	prob.delet.	N	0.36211135	None	None	N
A/V	0.2152	likely_benign	0.2218	benign	-0.061	Destabilizing	1.0	D	0.615	neutral	N	0.349065652	None	None	N
A/W	0.9924	likely_pathogenic	0.9893	pathogenic	-1.259	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
A/Y	0.9633	likely_pathogenic	0.9542	pathogenic	-0.686	Destabilizing	1.0	D	0.89	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.