TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27527	82804;82805;82806	chr2:178563553;178563552;178563551	chr2:179428280;179428279;179428278
N2AB	25886	77881;77882;77883	chr2:178563553;178563552;178563551	chr2:179428280;179428279;179428278
N2A	24959	75100;75101;75102	chr2:178563553;178563552;178563551	chr2:179428280;179428279;179428278
N2B	18462	55609;55610;55611	chr2:178563553;178563552;178563551	chr2:179428280;179428279;179428278
Novex-1	18587	55984;55985;55986	chr2:178563553;178563552;178563551	chr2:179428280;179428279;179428278
Novex-2	18654	56185;56186;56187	chr2:178563553;178563552;178563551	chr2:179428280;179428279;179428278
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-88
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.2999
• 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/P	rs202169004	-0.983	1.0	N	0.815	0.427	0.787995792498	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/P	rs202169004	-0.983	1.0	N	0.815	0.427	0.787995792498	gnomAD-4.0.0	1.43215E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.28671E-05	1.43271E-05	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	0.5611	ambiguous	0.5264	ambiguous	-2.015	Highly Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
L/C	0.5717	likely_pathogenic	0.5521	ambiguous	-1.143	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
L/D	0.9127	likely_pathogenic	0.9042	pathogenic	-1.928	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
L/E	0.6954	likely_pathogenic	0.6676	pathogenic	-1.754	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
L/F	0.4418	ambiguous	0.4218	ambiguous	-1.187	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
L/G	0.7114	likely_pathogenic	0.709	pathogenic	-2.484	Highly Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
L/H	0.5221	ambiguous	0.4973	ambiguous	-1.672	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/I	0.2258	likely_benign	0.1997	benign	-0.699	Destabilizing	0.999	D	0.501	neutral	None	None	None	None	N
L/K	0.4782	ambiguous	0.4333	ambiguous	-1.427	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
L/M	0.1921	likely_benign	0.1765	benign	-0.564	Destabilizing	1.0	D	0.701	prob.neutral	N	0.521903109	None	None	N
L/N	0.4925	ambiguous	0.4972	ambiguous	-1.651	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
L/P	0.6602	likely_pathogenic	0.6209	pathogenic	-1.115	Destabilizing	1.0	D	0.815	deleterious	N	0.499930327	None	None	N
L/Q	0.3041	likely_benign	0.2828	benign	-1.6	Destabilizing	1.0	D	0.797	deleterious	N	0.48354433	None	None	N
L/R	0.3054	likely_benign	0.285	benign	-1.06	Destabilizing	1.0	D	0.796	deleterious	N	0.502738558	None	None	N
L/S	0.5747	likely_pathogenic	0.5625	ambiguous	-2.321	Highly Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
L/T	0.2197	likely_benign	0.2027	benign	-2.007	Highly Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
L/V	0.1744	likely_benign	0.1574	benign	-1.115	Destabilizing	0.999	D	0.555	neutral	N	0.483037351	None	None	N
L/W	0.6595	likely_pathogenic	0.6376	pathogenic	-1.457	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
L/Y	0.7142	likely_pathogenic	0.6883	pathogenic	-1.134	Destabilizing	1.0	D	0.782	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.