TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21582	64969;64970;64971	chr2:178584897;178584896;178584895	chr2:179449624;179449623;179449622
N2AB	19941	60046;60047;60048	chr2:178584897;178584896;178584895	chr2:179449624;179449623;179449622
N2A	19014	57265;57266;57267	chr2:178584897;178584896;178584895	chr2:179449624;179449623;179449622
N2B	12517	37774;37775;37776	chr2:178584897;178584896;178584895	chr2:179449624;179449623;179449622
Novex-1	12642	38149;38150;38151	chr2:178584897;178584896;178584895	chr2:179449624;179449623;179449622
Novex-2	12709	38350;38351;38352	chr2:178584897;178584896;178584895	chr2:179449624;179449623;179449622
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-44
• Domain position: 24
• Structural Position: 25
• Q(SASA): 0.7746
• 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
H/R	rs770805220	-0.413	0.959	N	0.442	0.234	0.273938319068	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	9.97E-05	0	None	0	None	0	0	0
H/R	rs770805220	-0.413	0.959	N	0.442	0.234	0.273938319068	gnomAD-4.0.0	1.59222E-06	None	None	None	None	N	None	0	0	None	4.77008E-05	0	None	0	0	0	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
H/A	0.221	likely_benign	0.1928	benign	-0.214	Destabilizing	0.969	D	0.497	neutral	None	None	None	None	N
H/C	0.1771	likely_benign	0.1572	benign	0.647	Stabilizing	0.999	D	0.481	neutral	None	None	None	None	N
H/D	0.1787	likely_benign	0.1498	benign	-0.352	Destabilizing	0.015	N	0.225	neutral	N	0.338661732	None	None	N
H/E	0.2486	likely_benign	0.2118	benign	-0.27	Destabilizing	0.759	D	0.44	neutral	None	None	None	None	N
H/F	0.3098	likely_benign	0.275	benign	0.897	Stabilizing	0.997	D	0.535	neutral	None	None	None	None	N
H/G	0.2015	likely_benign	0.1761	benign	-0.571	Destabilizing	0.863	D	0.467	neutral	None	None	None	None	N
H/I	0.4068	ambiguous	0.3736	ambiguous	0.755	Stabilizing	0.997	D	0.54	neutral	None	None	None	None	N
H/K	0.1994	likely_benign	0.1793	benign	-0.133	Destabilizing	0.939	D	0.501	neutral	None	None	None	None	N
H/L	0.1306	likely_benign	0.1173	benign	0.755	Stabilizing	0.959	D	0.558	neutral	N	0.390167988	None	None	N
H/M	0.3668	ambiguous	0.3263	benign	0.591	Stabilizing	0.999	D	0.483	neutral	None	None	None	None	N
H/N	0.0727	likely_benign	0.0592	benign	-0.143	Destabilizing	0.061	N	0.155	neutral	N	0.308205539	None	None	N
H/P	0.3736	ambiguous	0.4266	ambiguous	0.455	Stabilizing	0.996	D	0.561	neutral	N	0.429918455	None	None	N
H/Q	0.1412	likely_benign	0.1249	benign	0.093	Stabilizing	0.959	D	0.473	neutral	N	0.342702115	None	None	N
H/R	0.1175	likely_benign	0.1116	benign	-0.847	Destabilizing	0.959	D	0.442	neutral	N	0.365117615	None	None	N
H/S	0.1796	likely_benign	0.152	benign	-0.009	Destabilizing	0.863	D	0.475	neutral	None	None	None	None	N
H/T	0.2483	likely_benign	0.2149	benign	0.169	Stabilizing	0.939	D	0.528	neutral	None	None	None	None	N
H/V	0.2944	likely_benign	0.2673	benign	0.455	Stabilizing	0.997	D	0.563	neutral	None	None	None	None	N
H/W	0.4671	ambiguous	0.4786	ambiguous	1.037	Stabilizing	0.999	D	0.521	neutral	None	None	None	None	N
H/Y	0.1124	likely_benign	0.1038	benign	1.191	Stabilizing	0.986	D	0.477	neutral	N	0.400462339	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.