TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7819	23680;23681;23682	chr2:178720187;178720186;178720185	chr2:179584914;179584913;179584912
N2AB	7502	22729;22730;22731	chr2:178720187;178720186;178720185	chr2:179584914;179584913;179584912
N2A	6575	19948;19949;19950	chr2:178720187;178720186;178720185	chr2:179584914;179584913;179584912
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-63
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.4748
• 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/Q	rs201420077	-0.177	0.468	D	0.455	0.191	None	gnomAD-2.1.1	1.96659E-04	None	None	None	None	I	None	0	2.83E-05	None	0	0	None	6.54E-05	None	7.99E-05	3.52676E-04	7.03037E-04
E/Q	rs201420077	-0.177	0.468	D	0.455	0.191	None	gnomAD-3.1.2	1.97119E-04	None	None	None	None	I	None	0	0	0	2.88184E-04	0	None	3.76506E-04	0	3.52837E-04	0	4.78927E-04
E/Q	rs201420077	-0.177	0.468	D	0.455	0.191	None	gnomAD-4.0.0	2.22478E-04	None	None	None	None	I	None	1.33472E-05	5.00083E-05	None	6.75676E-05	2.22836E-05	None	2.81241E-04	1.64474E-04	2.71248E-04	5.48992E-05	1.28098E-04

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	0.285	likely_benign	0.2817	benign	-0.526	Destabilizing	0.399	N	0.511	neutral	N	0.520495679	None	None	I
E/C	0.9601	likely_pathogenic	0.9606	pathogenic	-0.168	Destabilizing	0.986	D	0.699	prob.neutral	None	None	None	None	I
E/D	0.22	likely_benign	0.2318	benign	-0.531	Destabilizing	None	N	0.189	neutral	N	0.519572959	None	None	I
E/F	0.9348	likely_pathogenic	0.9384	pathogenic	-0.216	Destabilizing	0.972	D	0.645	neutral	None	None	None	None	I
E/G	0.3978	ambiguous	0.3878	ambiguous	-0.772	Destabilizing	0.688	D	0.533	neutral	N	0.49271113	None	None	I
E/H	0.6825	likely_pathogenic	0.7061	pathogenic	-0.054	Destabilizing	0.962	D	0.482	neutral	None	None	None	None	I
E/I	0.7232	likely_pathogenic	0.7231	pathogenic	0.107	Stabilizing	0.844	D	0.637	neutral	None	None	None	None	I
E/K	0.2999	likely_benign	0.3194	benign	0.199	Stabilizing	0.016	N	0.24	neutral	N	0.473107163	None	None	I
E/L	0.7405	likely_pathogenic	0.7374	pathogenic	0.107	Stabilizing	0.728	D	0.537	neutral	None	None	None	None	I
E/M	0.7704	likely_pathogenic	0.7672	pathogenic	0.237	Stabilizing	0.918	D	0.637	neutral	None	None	None	None	I
E/N	0.4945	ambiguous	0.5049	ambiguous	-0.27	Destabilizing	0.151	N	0.447	neutral	None	None	None	None	I
E/P	0.9885	likely_pathogenic	0.99	pathogenic	-0.083	Destabilizing	0.447	N	0.556	neutral	None	None	None	None	I
E/Q	0.218	likely_benign	0.2185	benign	-0.215	Destabilizing	0.468	N	0.455	neutral	D	0.531347391	None	None	I
E/R	0.4545	ambiguous	0.4969	ambiguous	0.468	Stabilizing	0.012	N	0.213	neutral	None	None	None	None	I
E/S	0.3126	likely_benign	0.3075	benign	-0.44	Destabilizing	0.468	N	0.438	neutral	None	None	None	None	I
E/T	0.3745	ambiguous	0.3705	ambiguous	-0.236	Destabilizing	0.549	D	0.499	neutral	None	None	None	None	I
E/V	0.468	ambiguous	0.4721	ambiguous	-0.083	Destabilizing	0.744	D	0.549	neutral	N	0.490887478	None	None	I
E/W	0.971	likely_pathogenic	0.9751	pathogenic	0.011	Stabilizing	0.997	D	0.697	prob.neutral	None	None	None	None	I
E/Y	0.8731	likely_pathogenic	0.8817	pathogenic	0.049	Stabilizing	0.99	D	0.633	neutral	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.