TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30852	92779;92780;92781	chr2:178549072;178549071;178549070	chr2:179413799;179413798;179413797
N2AB	29211	87856;87857;87858	chr2:178549072;178549071;178549070	chr2:179413799;179413798;179413797
N2A	28284	85075;85076;85077	chr2:178549072;178549071;178549070	chr2:179413799;179413798;179413797
N2B	21787	65584;65585;65586	chr2:178549072;178549071;178549070	chr2:179413799;179413798;179413797
Novex-1	21912	65959;65960;65961	chr2:178549072;178549071;178549070	chr2:179413799;179413798;179413797
Novex-2	21979	66160;66161;66162	chr2:178549072;178549071;178549070	chr2:179413799;179413798;179413797
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: Fn3-113
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.602
• 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/K	rs772252611	0.439	0.999	N	0.607	0.396	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
E/K	rs772252611	0.439	0.999	N	0.607	0.396	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs772252611	0.439	0.999	N	0.607	0.396	None	gnomAD-4.0.0	4.33768E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.93302E-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	0.1974	likely_benign	0.2151	benign	-0.424	Destabilizing	0.999	D	0.623	neutral	N	0.445799479	None	None	I
E/C	0.8838	likely_pathogenic	0.9023	pathogenic	-0.209	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
E/D	0.107	likely_benign	0.1072	benign	-0.375	Destabilizing	0.999	D	0.443	neutral	N	0.455725684	None	None	I
E/F	0.8885	likely_pathogenic	0.9166	pathogenic	-0.213	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	I
E/G	0.2292	likely_benign	0.2528	benign	-0.633	Destabilizing	1.0	D	0.642	neutral	N	0.481624206	None	None	I
E/H	0.6069	likely_pathogenic	0.6441	pathogenic	0.082	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	I
E/I	0.5993	likely_pathogenic	0.6468	pathogenic	0.1	Stabilizing	1.0	D	0.647	neutral	None	None	None	None	I
E/K	0.2702	likely_benign	0.3095	benign	0.16	Stabilizing	0.999	D	0.607	neutral	N	0.453648171	None	None	I
E/L	0.576	likely_pathogenic	0.6249	pathogenic	0.1	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	I
E/M	0.6361	likely_pathogenic	0.6787	pathogenic	0.115	Stabilizing	1.0	D	0.628	neutral	None	None	None	None	I
E/N	0.301	likely_benign	0.3099	benign	-0.185	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
E/P	0.3804	ambiguous	0.3831	ambiguous	-0.055	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	I
E/Q	0.2029	likely_benign	0.2175	benign	-0.137	Destabilizing	1.0	D	0.613	neutral	N	0.504615709	None	None	I
E/R	0.3871	ambiguous	0.4382	ambiguous	0.455	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
E/S	0.296	likely_benign	0.3159	benign	-0.359	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	I
E/T	0.358	ambiguous	0.3773	ambiguous	-0.189	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
E/V	0.3424	ambiguous	0.3858	ambiguous	-0.055	Destabilizing	1.0	D	0.695	prob.neutral	N	0.470517913	None	None	I
E/W	0.9464	likely_pathogenic	0.962	pathogenic	-0.04	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
E/Y	0.7575	likely_pathogenic	0.8034	pathogenic	0.028	Stabilizing	1.0	D	0.652	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.