TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5022	15289;15290;15291	chr2:178734860;178734859;178734858	chr2:179599587;179599586;179599585
N2AB	4705	14338;14339;14340	chr2:178734860;178734859;178734858	chr2:179599587;179599586;179599585
N2A	3778	11557;11558;11559	chr2:178734860;178734859;178734858	chr2:179599587;179599586;179599585
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-33
• Domain position: 42
• Structural Position: 58
• Q(SASA): 0.1648
• 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/F	rs931153562	None	0.982	D	0.692	0.553	0.642232531769	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/F	rs931153562	None	0.982	D	0.692	0.553	0.642232531769	gnomAD-4.0.0	6.57212E-06	None	None	None	None	N	None	2.41278E-05	0	None	0	0	None	0	0	0	0	0
L/V	rs931153562	-1.409	0.17	N	0.372	0.193	0.363356657567	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
L/V	rs931153562	-1.409	0.17	N	0.372	0.193	0.363356657567	gnomAD-4.0.0	1.5916E-06	None	None	None	None	N	None	5.65611E-05	0	None	0	0	None	0	0	0	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	0.7287	likely_pathogenic	0.738	pathogenic	-2.09	Highly Destabilizing	0.953	D	0.467	neutral	None	None	None	None	N
L/C	0.8021	likely_pathogenic	0.8158	pathogenic	-1.254	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
L/D	0.9833	likely_pathogenic	0.9818	pathogenic	-1.925	Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	N
L/E	0.9002	likely_pathogenic	0.9015	pathogenic	-1.737	Destabilizing	0.998	D	0.82	deleterious	None	None	None	None	N
L/F	0.3117	likely_benign	0.2932	benign	-1.196	Destabilizing	0.982	D	0.692	prob.neutral	D	0.61317489	None	None	N
L/G	0.9376	likely_pathogenic	0.9409	pathogenic	-2.575	Highly Destabilizing	0.998	D	0.808	deleterious	None	None	None	None	N
L/H	0.816	likely_pathogenic	0.8023	pathogenic	-1.74	Destabilizing	0.999	D	0.819	deleterious	D	0.705510991	None	None	N
L/I	0.07	likely_benign	0.0676	benign	-0.723	Destabilizing	0.046	N	0.389	neutral	N	0.448330142	None	None	N
L/K	0.8502	likely_pathogenic	0.8432	pathogenic	-1.493	Destabilizing	0.993	D	0.763	deleterious	None	None	None	None	N
L/M	0.1785	likely_benign	0.1829	benign	-0.621	Destabilizing	0.986	D	0.723	prob.delet.	None	None	None	None	N
L/N	0.9192	likely_pathogenic	0.9169	pathogenic	-1.729	Destabilizing	0.998	D	0.83	deleterious	None	None	None	None	N
L/P	0.9396	likely_pathogenic	0.9253	pathogenic	-1.156	Destabilizing	0.997	D	0.831	deleterious	D	0.653996328	None	None	N
L/Q	0.7167	likely_pathogenic	0.7118	pathogenic	-1.648	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
L/R	0.7801	likely_pathogenic	0.7675	pathogenic	-1.169	Destabilizing	0.997	D	0.797	deleterious	D	0.666555392	None	None	N
L/S	0.8969	likely_pathogenic	0.8972	pathogenic	-2.429	Highly Destabilizing	0.993	D	0.741	deleterious	None	None	None	None	N
L/T	0.7313	likely_pathogenic	0.7417	pathogenic	-2.093	Highly Destabilizing	0.986	D	0.675	prob.neutral	None	None	None	None	N
L/V	0.1041	likely_benign	0.1017	benign	-1.156	Destabilizing	0.17	N	0.372	neutral	N	0.520507819	None	None	N
L/W	0.6502	likely_pathogenic	0.6371	pathogenic	-1.442	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
L/Y	0.7181	likely_pathogenic	0.7238	pathogenic	-1.142	Destabilizing	0.998	D	0.771	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.