TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26918	80977;80978;80979	chr2:178565380;178565379;178565378	chr2:179430107;179430106;179430105
N2AB	25277	76054;76055;76056	chr2:178565380;178565379;178565378	chr2:179430107;179430106;179430105
N2A	24350	73273;73274;73275	chr2:178565380;178565379;178565378	chr2:179430107;179430106;179430105
N2B	17853	53782;53783;53784	chr2:178565380;178565379;178565378	chr2:179430107;179430106;179430105
Novex-1	17978	54157;54158;54159	chr2:178565380;178565379;178565378	chr2:179430107;179430106;179430105
Novex-2	18045	54358;54359;54360	chr2:178565380;178565379;178565378	chr2:179430107;179430106;179430105
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-139
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.4626
• 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	None	None	0.166	N	0.28	0.186	0.283371740733	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	0.0977	likely_benign	0.1071	benign	-0.294	Destabilizing	0.166	N	0.357	neutral	N	0.479379775	None	None	N
E/C	0.4925	ambiguous	0.5435	ambiguous	-0.126	Destabilizing	0.991	D	0.361	neutral	None	None	None	None	N
E/D	0.1147	likely_benign	0.1088	benign	-0.322	Destabilizing	0.166	N	0.275	neutral	D	0.52424806	None	None	N
E/F	0.3746	ambiguous	0.3991	ambiguous	-0.21	Destabilizing	0.818	D	0.422	neutral	None	None	None	None	N
E/G	0.1112	likely_benign	0.1195	benign	-0.471	Destabilizing	0.166	N	0.358	neutral	N	0.492714431	None	None	N
E/H	0.1925	likely_benign	0.2277	benign	0.144	Stabilizing	0.004	N	0.202	neutral	None	None	None	None	N
E/I	0.1054	likely_benign	0.1182	benign	0.129	Stabilizing	0.39	N	0.437	neutral	None	None	None	None	N
E/K	0.0746	likely_benign	0.0852	benign	0.289	Stabilizing	0.166	N	0.28	neutral	N	0.453481253	None	None	N
E/L	0.1317	likely_benign	0.1494	benign	0.129	Stabilizing	0.209	N	0.384	neutral	None	None	None	None	N
E/M	0.1687	likely_benign	0.1879	benign	0.102	Stabilizing	0.901	D	0.375	neutral	None	None	None	None	N
E/N	0.1269	likely_benign	0.1353	benign	-0.009	Destabilizing	0.004	N	0.177	neutral	None	None	None	None	N
E/P	0.7546	likely_pathogenic	0.7671	pathogenic	0.007	Stabilizing	0.722	D	0.419	neutral	None	None	None	None	N
E/Q	0.0696	likely_benign	0.0776	benign	0.027	Stabilizing	0.002	N	0.136	neutral	N	0.418733961	None	None	N
E/R	0.126	likely_benign	0.1505	benign	0.525	Stabilizing	0.39	N	0.217	neutral	None	None	None	None	N
E/S	0.1108	likely_benign	0.1203	benign	-0.158	Destabilizing	0.209	N	0.268	neutral	None	None	None	None	N
E/T	0.1152	likely_benign	0.1248	benign	-0.014	Destabilizing	0.345	N	0.364	neutral	None	None	None	None	N
E/V	0.0801	likely_benign	0.0885	benign	0.007	Stabilizing	0.003	N	0.235	neutral	N	0.467856059	None	None	N
E/W	0.6787	likely_pathogenic	0.7212	pathogenic	-0.09	Destabilizing	0.991	D	0.368	neutral	None	None	None	None	N
E/Y	0.3056	likely_benign	0.3349	benign	0.021	Stabilizing	0.818	D	0.455	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.