TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19849	59770;59771;59772	chr2:178592460;178592459;178592458	chr2:179457187;179457186;179457185
N2AB	18208	54847;54848;54849	chr2:178592460;178592459;178592458	chr2:179457187;179457186;179457185
N2A	17281	52066;52067;52068	chr2:178592460;178592459;178592458	chr2:179457187;179457186;179457185
N2B	10784	32575;32576;32577	chr2:178592460;178592459;178592458	chr2:179457187;179457186;179457185
Novex-1	10909	32950;32951;32952	chr2:178592460;178592459;178592458	chr2:179457187;179457186;179457185
Novex-2	10976	33151;33152;33153	chr2:178592460;178592459;178592458	chr2:179457187;179457186;179457185
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-119
• Domain position: 60
• Structural Position: 146
• Q(SASA): 1.0028
• 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
H/Q	None	None	0.642	N	0.258	0.093	0.0954503805726	gnomAD-4.0.0	1.5919E-06	None	None	None	None	I	None	0	0	None	0	2.77624E-05	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	0.4566	ambiguous	0.3165	benign	0.282	Stabilizing	0.495	N	0.32	neutral	None	None	None	None	I
H/C	0.3013	likely_benign	0.2278	benign	0.674	Stabilizing	0.995	D	0.289	neutral	None	None	None	None	I
H/D	0.5511	ambiguous	0.4306	ambiguous	0.064	Stabilizing	0.642	D	0.321	neutral	N	0.439180151	None	None	I
H/E	0.4859	ambiguous	0.3761	ambiguous	0.075	Stabilizing	0.329	N	0.315	neutral	None	None	None	None	I
H/F	0.4837	ambiguous	0.3861	ambiguous	0.799	Stabilizing	0.981	D	0.297	neutral	None	None	None	None	I
H/G	0.5327	ambiguous	0.4139	ambiguous	0.024	Stabilizing	0.704	D	0.321	neutral	None	None	None	None	I
H/I	0.5505	ambiguous	0.3924	ambiguous	0.929	Stabilizing	0.944	D	0.341	neutral	None	None	None	None	I
H/K	0.2298	likely_benign	0.1972	benign	0.249	Stabilizing	0.003	N	0.157	neutral	None	None	None	None	I
H/L	0.2164	likely_benign	0.1578	benign	0.929	Stabilizing	0.642	D	0.345	neutral	N	0.383420082	None	None	I
H/M	0.6567	likely_pathogenic	0.5245	ambiguous	0.726	Stabilizing	0.981	D	0.291	neutral	None	None	None	None	I
H/N	0.2922	likely_benign	0.2036	benign	0.295	Stabilizing	0.642	D	0.254	neutral	N	0.432619538	None	None	I
H/P	0.2283	likely_benign	0.1786	benign	0.739	Stabilizing	0.927	D	0.341	neutral	N	0.373877879	None	None	I
H/Q	0.2467	likely_benign	0.1863	benign	0.36	Stabilizing	0.642	D	0.258	neutral	N	0.406779731	None	None	I
H/R	0.0753	likely_benign	0.0703	benign	-0.253	Destabilizing	0.001	N	0.108	neutral	N	0.30592209	None	None	I
H/S	0.4721	ambiguous	0.339	benign	0.347	Stabilizing	0.495	N	0.301	neutral	None	None	None	None	I
H/T	0.5275	ambiguous	0.3708	ambiguous	0.455	Stabilizing	0.704	D	0.362	neutral	None	None	None	None	I
H/V	0.4497	ambiguous	0.3184	benign	0.739	Stabilizing	0.828	D	0.352	neutral	None	None	None	None	I
H/W	0.45	ambiguous	0.4133	ambiguous	0.755	Stabilizing	0.995	D	0.306	neutral	None	None	None	None	I
H/Y	0.1688	likely_benign	0.134	benign	1.069	Stabilizing	0.917	D	0.295	neutral	N	0.424461415	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.