TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6815	20668;20669;20670	chr2:178725879;178725878;178725877	chr2:179590606;179590605;179590604
N2AB	6498	19717;19718;19719	chr2:178725879;178725878;178725877	chr2:179590606;179590605;179590604
N2A	5571	16936;16937;16938	chr2:178725879;178725878;178725877	chr2:179590606;179590605;179590604
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: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-52
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.5786
• 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/Y	None	None	0.473	N	0.285	0.105	0.214338557667	gnomAD-4.0.0	1.5927E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02828E-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
H/A	0.2226	likely_benign	0.2129	benign	-0.571	Destabilizing	0.176	N	0.367	neutral	None	None	None	None	N
H/C	0.1723	likely_benign	0.1975	benign	0.008	Stabilizing	0.981	D	0.533	neutral	None	None	None	None	N
H/D	0.1776	likely_benign	0.1658	benign	-0.256	Destabilizing	0.642	D	0.43	neutral	N	0.375847188	None	None	N
H/E	0.215	likely_benign	0.2072	benign	-0.221	Destabilizing	0.329	N	0.273	neutral	None	None	None	None	N
H/F	0.2474	likely_benign	0.2345	benign	-0.167	Destabilizing	0.007	N	0.219	neutral	None	None	None	None	N
H/G	0.3016	likely_benign	0.2863	benign	-0.855	Destabilizing	0.495	N	0.448	neutral	None	None	None	None	N
H/I	0.1791	likely_benign	0.1887	benign	0.173	Stabilizing	0.007	N	0.358	neutral	None	None	None	None	N
H/K	0.1776	likely_benign	0.1849	benign	-0.502	Destabilizing	0.329	N	0.403	neutral	None	None	None	None	N
H/L	0.0929	likely_benign	0.0955	benign	0.173	Stabilizing	0.002	N	0.346	neutral	N	0.375193827	None	None	N
H/M	0.3725	ambiguous	0.3812	ambiguous	0.147	Stabilizing	0.893	D	0.544	neutral	None	None	None	None	N
H/N	0.0904	likely_benign	0.0807	benign	-0.291	Destabilizing	0.642	D	0.275	neutral	N	0.408170251	None	None	N
H/P	0.4482	ambiguous	0.4259	ambiguous	-0.052	Destabilizing	0.784	D	0.579	neutral	N	0.47231773	None	None	N
H/Q	0.1156	likely_benign	0.1125	benign	-0.222	Destabilizing	0.023	N	0.167	neutral	N	0.427910805	None	None	N
H/R	0.0778	likely_benign	0.0796	benign	-0.694	Destabilizing	0.473	N	0.307	neutral	N	0.412402634	None	None	N
H/S	0.1685	likely_benign	0.1569	benign	-0.421	Destabilizing	0.037	N	0.199	neutral	None	None	None	None	N
H/T	0.1903	likely_benign	0.1918	benign	-0.297	Destabilizing	0.329	N	0.447	neutral	None	None	None	None	N
H/V	0.1626	likely_benign	0.1666	benign	-0.052	Destabilizing	0.329	N	0.428	neutral	None	None	None	None	N
H/W	0.3765	ambiguous	0.3777	ambiguous	-0.074	Destabilizing	0.995	D	0.537	neutral	None	None	None	None	N
H/Y	0.0912	likely_benign	0.0873	benign	0.299	Stabilizing	0.473	N	0.285	neutral	N	0.423929137	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.