TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29473	88642;88643;88644	chr2:178555042;178555041;178555040	chr2:179419769;179419768;179419767
N2AB	27832	83719;83720;83721	chr2:178555042;178555041;178555040	chr2:179419769;179419768;179419767
N2A	26905	80938;80939;80940	chr2:178555042;178555041;178555040	chr2:179419769;179419768;179419767
N2B	20408	61447;61448;61449	chr2:178555042;178555041;178555040	chr2:179419769;179419768;179419767
Novex-1	20533	61822;61823;61824	chr2:178555042;178555041;178555040	chr2:179419769;179419768;179419767
Novex-2	20600	62023;62024;62025	chr2:178555042;178555041;178555040	chr2:179419769;179419768;179419767
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-146
• Domain position: 30
• Structural Position: 47
• Q(SASA): 0.355
• 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	rs1575552905	None	0.999	D	0.511	0.229	0.266843984389	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/D	rs1575552905	None	0.999	D	0.511	0.229	0.266843984389	gnomAD-4.0.0	2.56232E-06	None	None	None	None	N	None	0	1.69492E-05	None	0	0	None	0	0	2.39275E-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	0.2043	likely_benign	0.1789	benign	-0.653	Destabilizing	0.999	D	0.694	prob.neutral	N	0.49194364	None	None	N
E/C	0.826	likely_pathogenic	0.8153	pathogenic	-0.532	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/D	0.3189	likely_benign	0.2964	benign	-1.287	Destabilizing	0.999	D	0.511	neutral	D	0.522093189	None	None	N
E/F	0.7936	likely_pathogenic	0.7536	pathogenic	0.134	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
E/G	0.3661	ambiguous	0.3171	benign	-1.069	Destabilizing	1.0	D	0.725	prob.delet.	N	0.487102043	None	None	N
E/H	0.536	ambiguous	0.4886	ambiguous	-0.19	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
E/I	0.3533	ambiguous	0.3286	benign	0.498	Stabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
E/K	0.2315	likely_benign	0.1922	benign	-0.907	Destabilizing	0.999	D	0.597	neutral	N	0.44805679	None	None	N
E/L	0.4847	ambiguous	0.4393	ambiguous	0.498	Stabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
E/M	0.4823	ambiguous	0.4466	ambiguous	0.896	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/N	0.4887	ambiguous	0.4498	ambiguous	-1.449	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/P	0.9901	likely_pathogenic	0.9887	pathogenic	0.136	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/Q	0.1472	likely_benign	0.1307	benign	-1.23	Destabilizing	1.0	D	0.649	neutral	N	0.467162626	None	None	N
E/R	0.3658	ambiguous	0.3137	benign	-0.572	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/S	0.2761	likely_benign	0.2459	benign	-1.784	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
E/T	0.2328	likely_benign	0.2143	benign	-1.435	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/V	0.2218	likely_benign	0.2084	benign	0.136	Stabilizing	1.0	D	0.773	deleterious	N	0.471723084	None	None	N
E/W	0.9351	likely_pathogenic	0.9181	pathogenic	0.328	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/Y	0.7386	likely_pathogenic	0.6943	pathogenic	0.356	Stabilizing	1.0	D	0.813	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.