TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7998	24217;24218;24219	chr2:178719398;178719397;178719396	chr2:179584125;179584124;179584123
N2AB	7681	23266;23267;23268	chr2:178719398;178719397;178719396	chr2:179584125;179584124;179584123
N2A	6754	20485;20486;20487	chr2:178719398;178719397;178719396	chr2:179584125;179584124;179584123
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: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-65
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.4043
• 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/Q	rs1188351264	-0.888	0.497	N	0.561	0.282	0.611542178662	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
L/Q	rs1188351264	-0.888	0.497	N	0.561	0.282	0.611542178662	gnomAD-4.0.0	1.3685E-06	None	None	None	None	I	None	0	0	None	0	2.5194E-05	None	0	0	8.99541E-07	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
L/A	0.1047	likely_benign	0.1099	benign	-1.079	Destabilizing	0.157	N	0.391	neutral	None	None	None	None	I
L/C	0.3483	ambiguous	0.3508	ambiguous	-0.786	Destabilizing	0.909	D	0.447	neutral	None	None	None	None	I
L/D	0.4372	ambiguous	0.4582	ambiguous	-0.462	Destabilizing	0.726	D	0.631	neutral	None	None	None	None	I
L/E	0.1872	likely_benign	0.1991	benign	-0.503	Destabilizing	0.726	D	0.621	neutral	None	None	None	None	I
L/F	0.0958	likely_benign	0.1036	benign	-0.77	Destabilizing	0.567	D	0.337	neutral	None	None	None	None	I
L/G	0.2873	likely_benign	0.3038	benign	-1.33	Destabilizing	0.567	D	0.617	neutral	None	None	None	None	I
L/H	0.1195	likely_benign	0.1319	benign	-0.501	Destabilizing	0.968	D	0.667	neutral	None	None	None	None	I
L/I	0.0771	likely_benign	0.0771	benign	-0.502	Destabilizing	0.005	N	0.308	neutral	None	None	None	None	I
L/K	0.1393	likely_benign	0.1399	benign	-0.741	Destabilizing	0.567	D	0.541	neutral	None	None	None	None	I
L/M	0.1064	likely_benign	0.1095	benign	-0.503	Destabilizing	0.02	N	0.397	neutral	N	0.480413485	None	None	I
L/N	0.2573	likely_benign	0.2661	benign	-0.562	Destabilizing	0.726	D	0.629	neutral	None	None	None	None	I
L/P	0.1686	likely_benign	0.2079	benign	-0.661	Destabilizing	0.859	D	0.632	neutral	N	0.471369927	None	None	I
L/Q	0.0864	likely_benign	0.0886	benign	-0.744	Destabilizing	0.497	N	0.561	neutral	N	0.469657774	None	None	I
L/R	0.0951	likely_benign	0.0983	benign	-0.156	Destabilizing	0.497	N	0.56	neutral	N	0.495785582	None	None	I
L/S	0.1092	likely_benign	0.1144	benign	-1.1	Destabilizing	0.567	D	0.509	neutral	None	None	None	None	I
L/T	0.1053	likely_benign	0.1108	benign	-1.024	Destabilizing	0.157	N	0.393	neutral	None	None	None	None	I
L/V	0.0745	likely_benign	0.0755	benign	-0.661	Destabilizing	0.001	N	0.167	neutral	N	0.394503867	None	None	I
L/W	0.1509	likely_benign	0.1617	benign	-0.802	Destabilizing	0.968	D	0.671	neutral	None	None	None	None	I
L/Y	0.2212	likely_benign	0.2376	benign	-0.578	Destabilizing	0.726	D	0.392	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.