TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6696	20311;20312;20313	chr2:178727279;178727278;178727277	chr2:179592006;179592005;179592004
N2AB	6379	19360;19361;19362	chr2:178727279;178727278;178727277	chr2:179592006;179592005;179592004
N2A	5452	16579;16580;16581	chr2:178727279;178727278;178727277	chr2:179592006;179592005;179592004
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-51
• Domain position: 30
• Structural Position: 43
• Q(SASA): 0.6111
• Predicted PPI site: I

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
E/A	rs764124148	-0.14	0.008	N	0.419	0.272	0.294918367191	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
E/A	rs764124148	-0.14	0.008	N	0.419	0.272	0.294918367191	gnomAD-4.0.0	1.5928E-06	None	None	None	None	I	None	0	0	None	0	2.77593E-05	None	0	0	0	0	0
E/G	rs764124148	-0.504	0.063	N	0.459	0.312	0.35139820857	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
E/G	rs764124148	-0.504	0.063	N	0.459	0.312	0.35139820857	gnomAD-4.0.0	3.18561E-06	None	None	None	None	I	None	0	4.57959E-05	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
E/A	0.1339	likely_benign	0.1464	benign	-0.125	Destabilizing	0.008	N	0.419	neutral	N	0.514839143	None	None	I
E/C	0.8468	likely_pathogenic	0.8843	pathogenic	-0.273	Destabilizing	0.685	D	0.461	neutral	None	None	None	None	I
E/D	0.0839	likely_benign	0.0866	benign	-0.309	Destabilizing	None	N	0.191	neutral	N	0.482832401	None	None	I
E/F	0.7538	likely_pathogenic	0.7955	pathogenic	-0.041	Destabilizing	0.26	N	0.453	neutral	None	None	None	None	I
E/G	0.1812	likely_benign	0.1917	benign	-0.275	Destabilizing	0.063	N	0.459	neutral	N	0.493938898	None	None	I
E/H	0.413	ambiguous	0.4767	ambiguous	0.554	Stabilizing	0.201	N	0.335	neutral	None	None	None	None	I
E/I	0.3727	ambiguous	0.407	ambiguous	0.223	Stabilizing	0.011	N	0.449	neutral	None	None	None	None	I
E/K	0.1546	likely_benign	0.1875	benign	0.342	Stabilizing	0.036	N	0.321	neutral	N	0.516127222	None	None	I
E/L	0.3895	ambiguous	0.4324	ambiguous	0.223	Stabilizing	0.011	N	0.461	neutral	None	None	None	None	I
E/M	0.507	ambiguous	0.5454	ambiguous	-0.011	Destabilizing	0.029	N	0.438	neutral	None	None	None	None	I
E/N	0.1796	likely_benign	0.2097	benign	0.005	Stabilizing	0.005	N	0.34	neutral	None	None	None	None	I
E/P	0.2874	likely_benign	0.3058	benign	0.126	Stabilizing	None	N	0.171	neutral	None	None	None	None	I
E/Q	0.1395	likely_benign	0.1564	benign	0.039	Stabilizing	0.026	N	0.364	neutral	N	0.485541426	None	None	I
E/R	0.2494	likely_benign	0.2947	benign	0.654	Stabilizing	0.148	N	0.345	neutral	None	None	None	None	I
E/S	0.1712	likely_benign	0.1882	benign	-0.137	Destabilizing	0.013	N	0.299	neutral	None	None	None	None	I
E/T	0.2471	likely_benign	0.274	benign	-0.005	Destabilizing	0.036	N	0.41	neutral	None	None	None	None	I
E/V	0.2126	likely_benign	0.2284	benign	0.126	Stabilizing	None	N	0.341	neutral	N	0.50987604	None	None	I
E/W	0.9026	likely_pathogenic	0.925	pathogenic	0.056	Stabilizing	0.915	D	0.534	neutral	None	None	None	None	I
E/Y	0.5824	likely_pathogenic	0.6468	pathogenic	0.193	Stabilizing	0.741	D	0.445	neutral	None	None	None	None	I

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.