TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6777	20554;20555;20556	chr2:178725993;178725992;178725991	chr2:179590720;179590719;179590718
N2AB	6460	19603;19604;19605	chr2:178725993;178725992;178725991	chr2:179590720;179590719;179590718
N2A	5533	16822;16823;16824	chr2:178725993;178725992;178725991	chr2:179590720;179590719;179590718
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-52
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.3718
• 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/Q	rs761148465	-0.635	0.891	N	0.344	0.218	0.24896430686	gnomAD-2.1.1	3.75E-05	None	None	None	None	N	None	0	2.47402E-04	None	0	0	None	0	None	0	9.11E-06	0
E/Q	rs761148465	-0.635	0.891	N	0.344	0.218	0.24896430686	gnomAD-4.0.0	1.46414E-05	None	None	None	None	N	None	0	1.88226E-04	None	0	0	None	0	0	2.92174E-06	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	0.2453	likely_benign	0.2486	benign	-0.805	Destabilizing	0.454	N	0.368	neutral	N	0.447382	None	None	N
E/C	0.949	likely_pathogenic	0.95	pathogenic	-0.413	Destabilizing	0.998	D	0.409	neutral	None	None	None	None	N
E/D	0.1196	likely_benign	0.1054	benign	-0.859	Destabilizing	0.005	N	0.103	neutral	N	0.364939548	None	None	N
E/F	0.9133	likely_pathogenic	0.9044	pathogenic	-0.414	Destabilizing	0.991	D	0.405	neutral	None	None	None	None	N
E/G	0.3151	likely_benign	0.3107	benign	-1.113	Destabilizing	0.801	D	0.353	neutral	N	0.490923477	None	None	N
E/H	0.7453	likely_pathogenic	0.746	pathogenic	-0.572	Destabilizing	0.991	D	0.351	neutral	None	None	None	None	N
E/I	0.6823	likely_pathogenic	0.6674	pathogenic	0.018	Stabilizing	0.949	D	0.418	neutral	None	None	None	None	N
E/K	0.4145	ambiguous	0.4256	ambiguous	-0.551	Destabilizing	0.801	D	0.291	neutral	N	0.46829599	None	None	N
E/L	0.7007	likely_pathogenic	0.6833	pathogenic	0.018	Stabilizing	0.842	D	0.389	neutral	None	None	None	None	N
E/M	0.7362	likely_pathogenic	0.7273	pathogenic	0.362	Stabilizing	0.998	D	0.368	neutral	None	None	None	None	N
E/N	0.3837	ambiguous	0.3664	ambiguous	-0.885	Destabilizing	0.728	D	0.265	neutral	None	None	None	None	N
E/P	0.6168	likely_pathogenic	0.6074	pathogenic	-0.235	Destabilizing	0.974	D	0.339	neutral	None	None	None	None	N
E/Q	0.3055	likely_benign	0.3107	benign	-0.79	Destabilizing	0.891	D	0.344	neutral	N	0.475454035	None	None	N
E/R	0.5782	likely_pathogenic	0.5883	pathogenic	-0.247	Destabilizing	0.974	D	0.317	neutral	None	None	None	None	N
E/S	0.3012	likely_benign	0.289	benign	-1.147	Destabilizing	0.172	N	0.133	neutral	None	None	None	None	N
E/T	0.3838	ambiguous	0.3736	ambiguous	-0.905	Destabilizing	0.067	N	0.207	neutral	None	None	None	None	N
E/V	0.4133	ambiguous	0.4214	ambiguous	-0.235	Destabilizing	0.801	D	0.359	neutral	N	0.467989345	None	None	N
E/W	0.9698	likely_pathogenic	0.967	pathogenic	-0.199	Destabilizing	0.998	D	0.555	neutral	None	None	None	None	N
E/Y	0.8491	likely_pathogenic	0.8355	pathogenic	-0.193	Destabilizing	0.991	D	0.381	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.