TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33502	100729;100730;100731	chr2:178536243;178536242;178536241	chr2:179400970;179400969;179400968
N2AB	31861	95806;95807;95808	chr2:178536243;178536242;178536241	chr2:179400970;179400969;179400968
N2A	30934	93025;93026;93027	chr2:178536243;178536242;178536241	chr2:179400970;179400969;179400968
N2B	24437	73534;73535;73536	chr2:178536243;178536242;178536241	chr2:179400970;179400969;179400968
Novex-1	24562	73909;73910;73911	chr2:178536243;178536242;178536241	chr2:179400970;179400969;179400968
Novex-2	24629	74110;74111;74112	chr2:178536243;178536242;178536241	chr2:179400970;179400969;179400968
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-158
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1545
• 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
L/Q	rs1464765995	None	0.998	D	0.733	0.76	0.817378622091	gnomAD-4.0.0	1.59217E-06	None	None	None	None	N	None	0	0	None	0	2.77546E-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
L/A	0.9596	likely_pathogenic	0.9168	pathogenic	-2.019	Highly Destabilizing	0.99	D	0.563	neutral	None	None	None	None	N
L/C	0.9689	likely_pathogenic	0.941	pathogenic	-1.403	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9981	pathogenic	-1.328	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/E	0.9944	likely_pathogenic	0.9914	pathogenic	-1.174	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
L/F	0.8386	likely_pathogenic	0.8015	pathogenic	-1.153	Destabilizing	0.993	D	0.64	neutral	None	None	None	None	N
L/G	0.9914	likely_pathogenic	0.9841	pathogenic	-2.504	Highly Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
L/H	0.9935	likely_pathogenic	0.9902	pathogenic	-1.797	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
L/I	0.3073	likely_benign	0.2302	benign	-0.675	Destabilizing	0.009	N	0.274	neutral	None	None	None	None	N
L/K	0.9914	likely_pathogenic	0.9877	pathogenic	-1.263	Destabilizing	0.953	D	0.712	prob.delet.	None	None	None	None	N
L/M	0.4206	ambiguous	0.3911	ambiguous	-0.698	Destabilizing	0.968	D	0.638	neutral	D	0.553574748	None	None	N
L/N	0.9925	likely_pathogenic	0.9881	pathogenic	-1.334	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
L/P	0.9313	likely_pathogenic	0.7337	pathogenic	-1.097	Destabilizing	0.999	D	0.79	deleterious	N	0.480484214	None	None	N
L/Q	0.9842	likely_pathogenic	0.9765	pathogenic	-1.28	Destabilizing	0.998	D	0.733	prob.delet.	D	0.572783694	None	None	N
L/R	0.9892	likely_pathogenic	0.9842	pathogenic	-0.994	Destabilizing	0.998	D	0.722	prob.delet.	D	0.567040298	None	None	N
L/S	0.9936	likely_pathogenic	0.9879	pathogenic	-2.149	Highly Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
L/T	0.9661	likely_pathogenic	0.9393	pathogenic	-1.846	Destabilizing	0.99	D	0.695	prob.neutral	None	None	None	None	N
L/V	0.4534	ambiguous	0.3331	benign	-1.097	Destabilizing	0.036	N	0.368	neutral	D	0.550415524	None	None	N
L/W	0.9778	likely_pathogenic	0.9731	pathogenic	-1.347	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
L/Y	0.987	likely_pathogenic	0.9838	pathogenic	-1.064	Destabilizing	0.99	D	0.693	prob.neutral	None	None	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.