TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24366	73321;73322;73323	chr2:178573036;178573035;178573034	chr2:179437763;179437762;179437761
N2AB	22725	68398;68399;68400	chr2:178573036;178573035;178573034	chr2:179437763;179437762;179437761
N2A	21798	65617;65618;65619	chr2:178573036;178573035;178573034	chr2:179437763;179437762;179437761
N2B	15301	46126;46127;46128	chr2:178573036;178573035;178573034	chr2:179437763;179437762;179437761
Novex-1	15426	46501;46502;46503	chr2:178573036;178573035;178573034	chr2:179437763;179437762;179437761
Novex-2	15493	46702;46703;46704	chr2:178573036;178573035;178573034	chr2:179437763;179437762;179437761
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: Fn3-65
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.9527
• 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/K	rs1708815210	None	0.505	N	0.427	0.226	0.241078983079	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1708815210	None	0.505	N	0.427	0.226	0.241078983079	gnomAD-4.0.0	6.57523E-06	None	None	None	None	N	None	2.41336E-05	0	None	0	0	None	0	0	0	0	0
E/V	rs1708814132	None	0.879	N	0.435	0.317	0.425148423609	gnomAD-4.0.0	1.59269E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8602E-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	0.116	likely_benign	0.1166	benign	-0.048	Destabilizing	0.505	D	0.439	neutral	N	0.468842202	None	None	N
E/C	0.6637	likely_pathogenic	0.6759	pathogenic	-0.257	Destabilizing	0.991	D	0.549	neutral	None	None	None	None	N
E/D	0.0828	likely_benign	0.0875	benign	-0.285	Destabilizing	0.001	N	0.257	neutral	N	0.404732009	None	None	N
E/F	0.6248	likely_pathogenic	0.6213	pathogenic	-0.074	Destabilizing	0.967	D	0.489	neutral	None	None	None	None	N
E/G	0.0887	likely_benign	0.0848	benign	-0.17	Destabilizing	0.338	N	0.445	neutral	N	0.402345064	None	None	N
E/H	0.273	likely_benign	0.2816	benign	0.554	Stabilizing	0.906	D	0.446	neutral	None	None	None	None	N
E/I	0.3002	likely_benign	0.3102	benign	0.217	Stabilizing	0.906	D	0.493	neutral	None	None	None	None	N
E/K	0.094	likely_benign	0.0914	benign	0.343	Stabilizing	0.505	D	0.427	neutral	N	0.466705974	None	None	N
E/L	0.2773	likely_benign	0.2763	benign	0.217	Stabilizing	0.826	D	0.457	neutral	None	None	None	None	N
E/M	0.3264	likely_benign	0.3314	benign	-0.045	Destabilizing	0.991	D	0.492	neutral	None	None	None	None	N
E/N	0.1414	likely_benign	0.1484	benign	0.119	Stabilizing	0.01	N	0.331	neutral	None	None	None	None	N
E/P	0.4144	ambiguous	0.4243	ambiguous	0.147	Stabilizing	0.01	N	0.369	neutral	None	None	None	None	N
E/Q	0.1059	likely_benign	0.1071	benign	0.13	Stabilizing	0.782	D	0.407	neutral	N	0.494545936	None	None	N
E/R	0.1675	likely_benign	0.1619	benign	0.62	Stabilizing	0.826	D	0.419	neutral	None	None	None	None	N
E/S	0.1157	likely_benign	0.1211	benign	-0.039	Destabilizing	0.404	N	0.427	neutral	None	None	None	None	N
E/T	0.1371	likely_benign	0.1456	benign	0.067	Stabilizing	0.575	D	0.431	neutral	None	None	None	None	N
E/V	0.1845	likely_benign	0.1869	benign	0.147	Stabilizing	0.879	D	0.435	neutral	N	0.484369015	None	None	N
E/W	0.7568	likely_pathogenic	0.7512	pathogenic	-0.023	Destabilizing	0.991	D	0.577	neutral	None	None	None	None	N
E/Y	0.4708	ambiguous	0.4713	ambiguous	0.149	Stabilizing	0.967	D	0.486	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.