TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6229	18910;18911;18912	chr2:178729471;178729470;178729469	chr2:179594198;179594197;179594196
N2AB	5912	17959;17960;17961	chr2:178729471;178729470;178729469	chr2:179594198;179594197;179594196
N2A	4985	15178;15179;15180	chr2:178729471;178729470;178729469	chr2:179594198;179594197;179594196
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-46
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.8326
• 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/D	rs376583582	None	0.22	N	0.581	0.115	0.258779203287	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs376583582	None	0.22	N	0.581	0.115	0.258779203287	gnomAD-4.0.0	3.84422E-06	None	None	None	None	I	None	5.07546E-05	0	None	0	0	None	0	0	0	0	0
E/G	None	None	0.22	N	0.602	0.468	0.501810158561	gnomAD-4.0.0	1.36858E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.31367E-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
E/A	0.1377	likely_benign	0.1511	benign	-0.282	Destabilizing	0.124	N	0.603	neutral	D	0.534753055	None	None	I
E/C	0.7882	likely_pathogenic	0.8054	pathogenic	-0.01	Destabilizing	0.968	D	0.738	prob.delet.	None	None	None	None	I
E/D	0.1297	likely_benign	0.14	benign	-0.34	Destabilizing	0.22	N	0.581	neutral	N	0.519687602	None	None	I
E/F	0.6215	likely_pathogenic	0.6465	pathogenic	-0.157	Destabilizing	0.89	D	0.717	prob.delet.	None	None	None	None	I
E/G	0.1819	likely_benign	0.1962	benign	-0.467	Destabilizing	0.22	N	0.602	neutral	N	0.508182039	None	None	I
E/H	0.2747	likely_benign	0.2943	benign	0.126	Stabilizing	0.567	D	0.651	neutral	None	None	None	None	I
E/I	0.2686	likely_benign	0.2857	benign	0.165	Stabilizing	0.726	D	0.723	prob.delet.	None	None	None	None	I
E/K	0.1094	likely_benign	0.1081	benign	0.492	Stabilizing	0.001	N	0.205	neutral	N	0.49977369	None	None	I
E/L	0.2867	likely_benign	0.3185	benign	0.165	Stabilizing	0.567	D	0.604	neutral	None	None	None	None	I
E/M	0.35	ambiguous	0.371	ambiguous	0.193	Stabilizing	0.909	D	0.717	prob.delet.	None	None	None	None	I
E/N	0.2092	likely_benign	0.2186	benign	0.082	Stabilizing	0.567	D	0.609	neutral	None	None	None	None	I
E/P	0.807	likely_pathogenic	0.8549	pathogenic	0.036	Stabilizing	0.726	D	0.681	prob.neutral	None	None	None	None	I
E/Q	0.0993	likely_benign	0.1072	benign	0.125	Stabilizing	0.002	N	0.249	neutral	N	0.510990761	None	None	I
E/R	0.1667	likely_benign	0.1661	benign	0.659	Stabilizing	0.157	N	0.605	neutral	None	None	None	None	I
E/S	0.1617	likely_benign	0.1723	benign	-0.032	Destabilizing	0.157	N	0.575	neutral	None	None	None	None	I
E/T	0.1548	likely_benign	0.1666	benign	0.128	Stabilizing	0.567	D	0.631	neutral	None	None	None	None	I
E/V	0.1618	likely_benign	0.1766	benign	0.036	Stabilizing	0.497	N	0.617	neutral	D	0.529712595	None	None	I
E/W	0.7848	likely_pathogenic	0.8069	pathogenic	-0.012	Destabilizing	0.968	D	0.733	prob.delet.	None	None	None	None	I
E/Y	0.4848	ambiguous	0.5088	ambiguous	0.093	Stabilizing	0.726	D	0.734	prob.delet.	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.