TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14804	44635;44636;44637	chr2:178629315;178629314;178629313	chr2:179494042;179494041;179494040
N2AB	13163	39712;39713;39714	chr2:178629315;178629314;178629313	chr2:179494042;179494041;179494040
N2A	12236	36931;36932;36933	chr2:178629315;178629314;178629313	chr2:179494042;179494041;179494040
N2B	5739	17440;17441;17442	chr2:178629315;178629314;178629313	chr2:179494042;179494041;179494040
Novex-1	5864	17815;17816;17817	chr2:178629315;178629314;178629313	chr2:179494042;179494041;179494040
Novex-2	5931	18016;18017;18018	chr2:178629315;178629314;178629313	chr2:179494042;179494041;179494040
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-99
• Domain position: 40
• Structural Position: 59
• Q(SASA): 0.7585
• 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/V	None	None	1.0	N	0.694	0.492	0.688307381067	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1217	likely_benign	0.1233	benign	-0.117	Destabilizing	0.999	D	0.669	neutral	D	0.5431021	None	None	N
E/C	0.7877	likely_pathogenic	0.7817	pathogenic	-0.351	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
E/D	0.1251	likely_benign	0.1255	benign	-0.396	Destabilizing	0.999	D	0.491	neutral	N	0.508330597	None	None	N
E/F	0.551	ambiguous	0.5866	pathogenic	0.094	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
E/G	0.1548	likely_benign	0.1624	benign	-0.293	Destabilizing	1.0	D	0.648	neutral	D	0.536866685	None	None	N
E/H	0.3893	ambiguous	0.4019	ambiguous	0.699	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/I	0.2011	likely_benign	0.2167	benign	0.307	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/K	0.1425	likely_benign	0.1558	benign	0.368	Stabilizing	0.999	D	0.639	neutral	N	0.482672908	None	None	N
E/L	0.2174	likely_benign	0.2194	benign	0.307	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/M	0.3115	likely_benign	0.3146	benign	0.022	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	N
E/N	0.2215	likely_benign	0.2396	benign	-0.144	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/P	0.3492	ambiguous	0.3551	ambiguous	0.185	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/Q	0.1179	likely_benign	0.1195	benign	-0.079	Destabilizing	1.0	D	0.585	neutral	N	0.493704679	None	None	N
E/R	0.249	likely_benign	0.261	benign	0.729	Stabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
E/S	0.1655	likely_benign	0.1728	benign	-0.25	Destabilizing	0.999	D	0.626	neutral	None	None	None	None	N
E/T	0.1672	likely_benign	0.176	benign	-0.09	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/V	0.122	likely_benign	0.1272	benign	0.185	Stabilizing	1.0	D	0.694	prob.neutral	N	0.51391892	None	None	N
E/W	0.8343	likely_pathogenic	0.855	pathogenic	0.224	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
E/Y	0.473	ambiguous	0.5056	ambiguous	0.338	Stabilizing	1.0	D	0.649	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.