TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6508	19747;19748;19749	chr2:178728302;178728301;178728300	chr2:179593029;179593028;179593027
N2AB	6191	18796;18797;18798	chr2:178728302;178728301;178728300	chr2:179593029;179593028;179593027
N2A	5264	16015;16016;16017	chr2:178728302;178728301;178728300	chr2:179593029;179593028;179593027
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: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-49
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.7882
• 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
L/V	None	None	0.948	N	0.487	0.217	0.536334086147	gnomAD-4.0.0	1.59281E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02847E-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
L/A	0.2882	likely_benign	0.2139	benign	-0.515	Destabilizing	0.992	D	0.449	neutral	None	None	None	None	I
L/C	0.7303	likely_pathogenic	0.6372	pathogenic	-0.776	Destabilizing	1.0	D	0.399	neutral	None	None	None	None	I
L/D	0.6847	likely_pathogenic	0.5232	ambiguous	-0.139	Destabilizing	0.999	D	0.551	neutral	None	None	None	None	I
L/E	0.344	ambiguous	0.2437	benign	-0.218	Destabilizing	0.999	D	0.548	neutral	None	None	None	None	I
L/F	0.1404	likely_benign	0.1241	benign	-0.534	Destabilizing	0.998	D	0.46	neutral	N	0.488744203	None	None	I
L/G	0.5815	likely_pathogenic	0.4835	ambiguous	-0.658	Destabilizing	0.999	D	0.551	neutral	None	None	None	None	I
L/H	0.2616	likely_benign	0.2227	benign	0.049	Stabilizing	1.0	D	0.553	neutral	N	0.49836818	None	None	I
L/I	0.1254	likely_benign	0.1025	benign	-0.256	Destabilizing	0.733	D	0.265	neutral	D	0.527997654	None	None	I
L/K	0.3361	likely_benign	0.2558	benign	-0.373	Destabilizing	0.999	D	0.459	neutral	None	None	None	None	I
L/M	0.1478	likely_benign	0.1337	benign	-0.542	Destabilizing	0.999	D	0.475	neutral	None	None	None	None	I
L/N	0.412	ambiguous	0.329	benign	-0.244	Destabilizing	1.0	D	0.557	neutral	None	None	None	None	I
L/P	0.2978	likely_benign	0.1826	benign	-0.312	Destabilizing	0.391	N	0.392	neutral	N	0.350073591	None	None	I
L/Q	0.1738	likely_benign	0.1353	benign	-0.41	Destabilizing	1.0	D	0.459	neutral	None	None	None	None	I
L/R	0.2544	likely_benign	0.2019	benign	0.103	Stabilizing	0.999	D	0.463	neutral	N	0.521551684	None	None	I
L/S	0.2371	likely_benign	0.1736	benign	-0.671	Destabilizing	0.999	D	0.451	neutral	None	None	None	None	I
L/T	0.2887	likely_benign	0.2152	benign	-0.641	Destabilizing	0.999	D	0.413	neutral	None	None	None	None	I
L/V	0.1274	likely_benign	0.1036	benign	-0.312	Destabilizing	0.948	D	0.487	neutral	N	0.509411893	None	None	I
L/W	0.2985	likely_benign	0.2414	benign	-0.561	Destabilizing	1.0	D	0.535	neutral	None	None	None	None	I
L/Y	0.3706	ambiguous	0.3151	benign	-0.32	Destabilizing	1.0	D	0.404	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.