TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8490	25693;25694;25695	chr2:178717266;178717265;178717264	chr2:179581993;179581992;179581991
N2AB	8173	24742;24743;24744	chr2:178717266;178717265;178717264	chr2:179581993;179581992;179581991
N2A	7246	21961;21962;21963	chr2:178717266;178717265;178717264	chr2:179581993;179581992;179581991
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-70
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.121
• 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/S	None	None	0.021	N	0.31	0.08	0.159798565429	gnomAD-4.0.0	3.42136E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7343E-04	0	4.638E-05	0
A/T	rs1411592951	-0.794	0.062	N	0.445	0.047	0.184867976434	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
A/T	rs1411592951	-0.794	0.062	N	0.445	0.047	0.184867976434	gnomAD-4.0.0	1.36854E-06	None	None	None	None	N	None	0	2.23644E-05	None	0	0	None	0	0	8.99548E-07	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	0.726	likely_pathogenic	0.5994	pathogenic	-0.703	Destabilizing	0.999	D	0.64	neutral	None	None	None	None	N
A/D	0.7427	likely_pathogenic	0.6006	pathogenic	-2.156	Highly Destabilizing	0.884	D	0.685	prob.neutral	N	0.45484274	None	None	N
A/E	0.5789	likely_pathogenic	0.4302	ambiguous	-1.899	Destabilizing	0.876	D	0.618	neutral	None	None	None	None	N
A/F	0.4191	ambiguous	0.3247	benign	-0.337	Destabilizing	0.214	N	0.538	neutral	None	None	None	None	N
A/G	0.2149	likely_benign	0.18	benign	-1.224	Destabilizing	0.425	N	0.571	neutral	N	0.510714962	None	None	N
A/H	0.7078	likely_pathogenic	0.5632	ambiguous	-1.986	Destabilizing	0.996	D	0.643	neutral	None	None	None	None	N
A/I	0.4331	ambiguous	0.3311	benign	0.749	Stabilizing	0.95	D	0.663	neutral	None	None	None	None	N
A/K	0.7986	likely_pathogenic	0.6482	pathogenic	-0.681	Destabilizing	0.95	D	0.611	neutral	None	None	None	None	N
A/L	0.2965	likely_benign	0.2225	benign	0.749	Stabilizing	0.886	D	0.607	neutral	None	None	None	None	N
A/M	0.2921	likely_benign	0.2326	benign	0.331	Stabilizing	0.886	D	0.563	neutral	None	None	None	None	N
A/N	0.491	ambiguous	0.3676	ambiguous	-1.14	Destabilizing	0.805	D	0.689	prob.neutral	None	None	None	None	N
A/P	0.9904	likely_pathogenic	0.9809	pathogenic	0.311	Stabilizing	0.982	D	0.689	prob.neutral	N	0.46636363	None	None	N
A/Q	0.5245	ambiguous	0.4083	ambiguous	-0.803	Destabilizing	0.772	D	0.477	neutral	None	None	None	None	N
A/R	0.7094	likely_pathogenic	0.5575	ambiguous	-1.099	Destabilizing	0.992	D	0.682	prob.neutral	None	None	None	None	N
A/S	0.1182	likely_benign	0.1028	benign	-1.493	Destabilizing	0.021	N	0.31	neutral	N	0.406145013	None	None	N
A/T	0.1436	likely_benign	0.1113	benign	-1.097	Destabilizing	0.062	N	0.445	neutral	N	0.411377474	None	None	N
A/V	0.2277	likely_benign	0.1759	benign	0.311	Stabilizing	0.687	D	0.569	neutral	N	0.438564076	None	None	N
A/W	0.8702	likely_pathogenic	0.7846	pathogenic	-1.276	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
A/Y	0.6176	likely_pathogenic	0.4876	ambiguous	-0.619	Destabilizing	0.985	D	0.677	prob.neutral	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.