TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18744	56455;56456;56457	chr2:178599671;178599670;178599669	chr2:179464398;179464397;179464396
N2AB	17103	51532;51533;51534	chr2:178599671;178599670;178599669	chr2:179464398;179464397;179464396
N2A	16176	48751;48752;48753	chr2:178599671;178599670;178599669	chr2:179464398;179464397;179464396
N2B	9679	29260;29261;29262	chr2:178599671;178599670;178599669	chr2:179464398;179464397;179464396
Novex-1	9804	29635;29636;29637	chr2:178599671;178599670;178599669	chr2:179464398;179464397;179464396
Novex-2	9871	29836;29837;29838	chr2:178599671;178599670;178599669	chr2:179464398;179464397;179464396
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-116
• Domain position: 57
• Structural Position: 131
• Q(SASA): 0.3993
• 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
D/A	None	None	0.896	N	0.369	0.298	0.290962096972	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	0	3.66327E-05

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
D/A	0.1881	likely_benign	0.1446	benign	-0.009	Destabilizing	0.896	D	0.369	neutral	N	0.499711322	None	None	I
D/C	0.6852	likely_pathogenic	0.5908	pathogenic	-0.093	Destabilizing	0.999	D	0.545	neutral	None	None	None	None	I
D/E	0.1522	likely_benign	0.1248	benign	-0.256	Destabilizing	0.011	N	0.11	neutral	N	0.482066924	None	None	I
D/F	0.7191	likely_pathogenic	0.6229	pathogenic	-0.056	Destabilizing	0.996	D	0.485	neutral	None	None	None	None	I
D/G	0.14	likely_benign	0.1071	benign	-0.136	Destabilizing	0.896	D	0.337	neutral	N	0.467556044	None	None	I
D/H	0.3508	ambiguous	0.2644	benign	0.468	Stabilizing	0.984	D	0.388	neutral	N	0.512891263	None	None	I
D/I	0.5827	likely_pathogenic	0.4538	ambiguous	0.258	Stabilizing	0.988	D	0.481	neutral	None	None	None	None	I
D/K	0.3533	ambiguous	0.255	benign	0.442	Stabilizing	0.851	D	0.34	neutral	None	None	None	None	I
D/L	0.5065	ambiguous	0.4033	ambiguous	0.258	Stabilizing	0.976	D	0.421	neutral	None	None	None	None	I
D/M	0.6761	likely_pathogenic	0.5786	pathogenic	0.105	Stabilizing	0.999	D	0.487	neutral	None	None	None	None	I
D/N	0.1043	likely_benign	0.09	benign	0.164	Stabilizing	0.896	D	0.383	neutral	N	0.492918635	None	None	I
D/P	0.596	likely_pathogenic	0.468	ambiguous	0.188	Stabilizing	0.988	D	0.358	neutral	None	None	None	None	I
D/Q	0.3412	ambiguous	0.2585	benign	0.185	Stabilizing	0.307	N	0.145	neutral	None	None	None	None	I
D/R	0.412	ambiguous	0.3062	benign	0.651	Stabilizing	0.976	D	0.394	neutral	None	None	None	None	I
D/S	0.1429	likely_benign	0.1131	benign	0.082	Stabilizing	0.919	D	0.303	neutral	None	None	None	None	I
D/T	0.3156	likely_benign	0.24	benign	0.189	Stabilizing	0.919	D	0.373	neutral	None	None	None	None	I
D/V	0.3857	ambiguous	0.2854	benign	0.188	Stabilizing	0.984	D	0.413	neutral	N	0.503271702	None	None	I
D/W	0.8852	likely_pathogenic	0.8402	pathogenic	-0.002	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	I
D/Y	0.3344	likely_benign	0.2615	benign	0.168	Stabilizing	0.995	D	0.485	neutral	N	0.461429787	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.