TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3875	11848;11849;11850	chr2:178741610;178741609;178741608	chr2:179606337;179606336;179606335
N2AB	3558	10897;10898;10899	chr2:178741610;178741609;178741608	chr2:179606337;179606336;179606335
N2A	None	None	chr2:None	chr2:None
N2B	3512	10759;10760;10761	chr2:178741610;178741609;178741608	chr2:179606337;179606336;179606335
Novex-1	3637	11134;11135;11136	chr2:178741610;178741609;178741608	chr2:179606337;179606336;179606335
Novex-2	3704	11335;11336;11337	chr2:178741610;178741609;178741608	chr2:179606337;179606336;179606335
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-27
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.0736
• 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	None	None	0.055	N	0.664	0.113	None	gnomAD-4.0.0	1.59122E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85814E-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
H/A	0.5358	ambiguous	0.5509	ambiguous	-1.671	Destabilizing	0.014	N	0.709	prob.delet.	None	None	None	None	N
H/C	0.1759	likely_benign	0.1911	benign	-1.109	Destabilizing	None	N	0.663	neutral	None	None	None	None	N
H/D	0.501	ambiguous	0.522	ambiguous	-1.495	Destabilizing	0.106	N	0.757	deleterious	N	0.451338306	None	None	N
H/E	0.6048	likely_pathogenic	0.5936	pathogenic	-1.305	Destabilizing	0.061	N	0.552	neutral	None	None	None	None	N
H/F	0.3237	likely_benign	0.3327	benign	0.103	Stabilizing	None	N	0.492	neutral	None	None	None	None	N
H/G	0.6213	likely_pathogenic	0.6291	pathogenic	-2.093	Highly Destabilizing	0.061	N	0.703	prob.neutral	None	None	None	None	N
H/I	0.4538	ambiguous	0.4485	ambiguous	-0.431	Destabilizing	0.016	N	0.707	prob.neutral	None	None	None	None	N
H/K	0.531	ambiguous	0.5161	ambiguous	-1.12	Destabilizing	0.072	N	0.736	prob.delet.	None	None	None	None	N
H/L	0.2208	likely_benign	0.2279	benign	-0.431	Destabilizing	0.005	N	0.725	prob.delet.	N	0.447529795	None	None	N
H/M	0.6958	likely_pathogenic	0.6933	pathogenic	-0.759	Destabilizing	0.356	N	0.765	deleterious	None	None	None	None	N
H/N	0.1798	likely_benign	0.1786	benign	-1.697	Destabilizing	0.106	N	0.609	neutral	N	0.453458555	None	None	N
H/P	0.6913	likely_pathogenic	0.7252	pathogenic	-0.833	Destabilizing	0.266	N	0.782	deleterious	N	0.44018006	None	None	N
H/Q	0.3716	ambiguous	0.3505	ambiguous	-1.296	Destabilizing	0.106	N	0.672	neutral	N	0.450521399	None	None	N
H/R	0.2008	likely_benign	0.2016	benign	-1.296	Destabilizing	0.055	N	0.664	neutral	N	0.450896776	None	None	N
H/S	0.3929	ambiguous	0.4063	ambiguous	-1.896	Destabilizing	0.031	N	0.689	prob.neutral	None	None	None	None	N
H/T	0.4838	ambiguous	0.4781	ambiguous	-1.584	Destabilizing	0.031	N	0.694	prob.neutral	None	None	None	None	N
H/V	0.4179	ambiguous	0.4161	ambiguous	-0.833	Destabilizing	0.031	N	0.709	prob.delet.	None	None	None	None	N
H/W	0.5131	ambiguous	0.5584	ambiguous	0.647	Stabilizing	0.356	N	0.765	deleterious	None	None	None	None	N
H/Y	0.0711	likely_benign	0.0768	benign	0.528	Stabilizing	None	N	0.268	neutral	N	0.423630029	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.