TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27828	83707;83708;83709	chr2:178562650;178562649;178562648	chr2:179427377;179427376;179427375
N2AB	26187	78784;78785;78786	chr2:178562650;178562649;178562648	chr2:179427377;179427376;179427375
N2A	25260	76003;76004;76005	chr2:178562650;178562649;178562648	chr2:179427377;179427376;179427375
N2B	18763	56512;56513;56514	chr2:178562650;178562649;178562648	chr2:179427377;179427376;179427375
Novex-1	18888	56887;56888;56889	chr2:178562650;178562649;178562648	chr2:179427377;179427376;179427375
Novex-2	18955	57088;57089;57090	chr2:178562650;178562649;178562648	chr2:179427377;179427376;179427375
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: Fn3-90
• Domain position: 63
• Structural Position: 94
• Q(SASA): 0.3651
• 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
E/D	rs1234125693	-0.477	0.005	N	0.124	0.1	0.203808441222	gnomAD-2.1.1	4.25E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.75E-05	None	0	0	0
E/D	rs1234125693	-0.477	0.005	N	0.124	0.1	0.203808441222	gnomAD-4.0.0	1.625E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.5063E-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
E/A	0.147	likely_benign	0.1386	benign	-0.697	Destabilizing	0.454	N	0.419	neutral	N	0.477000326	None	None	N
E/C	0.7148	likely_pathogenic	0.6972	pathogenic	-0.224	Destabilizing	0.998	D	0.571	neutral	None	None	None	None	N
E/D	0.0707	likely_benign	0.0665	benign	-0.663	Destabilizing	0.005	N	0.124	neutral	N	0.391440211	None	None	N
E/F	0.7159	likely_pathogenic	0.7054	pathogenic	-0.373	Destabilizing	0.974	D	0.576	neutral	None	None	None	None	N
E/G	0.1177	likely_benign	0.1154	benign	-0.958	Destabilizing	0.625	D	0.459	neutral	N	0.460108076	None	None	N
E/H	0.4051	ambiguous	0.409	ambiguous	-0.331	Destabilizing	0.991	D	0.453	neutral	None	None	None	None	N
E/I	0.3751	ambiguous	0.3484	ambiguous	-0.018	Destabilizing	0.949	D	0.569	neutral	None	None	None	None	N
E/K	0.1927	likely_benign	0.2023	benign	-0.006	Destabilizing	0.801	D	0.363	neutral	N	0.44902429	None	None	N
E/L	0.3873	ambiguous	0.3664	ambiguous	-0.018	Destabilizing	0.728	D	0.546	neutral	None	None	None	None	N
E/M	0.4622	ambiguous	0.4507	ambiguous	0.252	Stabilizing	0.998	D	0.541	neutral	None	None	None	None	N
E/N	0.1609	likely_benign	0.1553	benign	-0.456	Destabilizing	0.728	D	0.343	neutral	None	None	None	None	N
E/P	0.3133	likely_benign	0.2943	benign	-0.224	Destabilizing	0.974	D	0.538	neutral	None	None	None	None	N
E/Q	0.1493	likely_benign	0.1547	benign	-0.391	Destabilizing	0.891	D	0.426	neutral	N	0.460953438	None	None	N
E/R	0.3047	likely_benign	0.3172	benign	0.246	Stabilizing	0.974	D	0.443	neutral	None	None	None	None	N
E/S	0.1386	likely_benign	0.1313	benign	-0.641	Destabilizing	0.08	N	0.125	neutral	None	None	None	None	N
E/T	0.1669	likely_benign	0.1543	benign	-0.423	Destabilizing	0.067	N	0.253	neutral	None	None	None	None	N
E/V	0.2404	likely_benign	0.2248	benign	-0.224	Destabilizing	0.669	D	0.531	neutral	N	0.481040708	None	None	N
E/W	0.8602	likely_pathogenic	0.8616	pathogenic	-0.126	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	N
E/Y	0.5593	ambiguous	0.5578	ambiguous	-0.113	Destabilizing	0.991	D	0.553	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.