TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8004	24235;24236;24237	chr2:178719380;178719379;178719378	chr2:179584107;179584106;179584105
N2AB	7687	23284;23285;23286	chr2:178719380;178719379;178719378	chr2:179584107;179584106;179584105
N2A	6760	20503;20504;20505	chr2:178719380;178719379;178719378	chr2:179584107;179584106;179584105
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: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-65
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1558
• 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/W	rs1274821392	-1.743	1.0	D	0.836	0.753	0.882730752339	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	1.44928E-04	None	0	0	None	0	None	0	0	0
L/W	rs1274821392	-1.743	1.0	D	0.836	0.753	0.882730752339	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	1.30959E-04	0	0	0	None	0	0	0	0	0
L/W	rs1274821392	-1.743	1.0	D	0.836	0.753	0.882730752339	gnomAD-4.0.0	8.96797E-06	None	None	None	None	N	None	0	1.01685E-04	None	0	0	None	0	0	0	0	2.84446E-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	0.6834	likely_pathogenic	0.7719	pathogenic	-2.224	Highly Destabilizing	0.97	D	0.704	prob.neutral	None	None	None	None	N
L/C	0.8289	likely_pathogenic	0.8804	pathogenic	-1.504	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
L/D	0.9894	likely_pathogenic	0.9938	pathogenic	-3.075	Highly Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
L/E	0.9271	likely_pathogenic	0.9536	pathogenic	-2.778	Highly Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
L/F	0.1105	likely_benign	0.1346	benign	-1.428	Destabilizing	0.989	D	0.696	prob.neutral	N	0.496176024	None	None	N
L/G	0.9145	likely_pathogenic	0.9467	pathogenic	-2.772	Highly Destabilizing	0.996	D	0.876	deleterious	None	None	None	None	N
L/H	0.7864	likely_pathogenic	0.8567	pathogenic	-2.527	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/I	0.1598	likely_benign	0.19	benign	-0.587	Destabilizing	0.304	N	0.265	neutral	None	None	None	None	N
L/K	0.8806	likely_pathogenic	0.9136	pathogenic	-1.816	Destabilizing	0.996	D	0.84	deleterious	None	None	None	None	N
L/M	0.092	likely_benign	0.1013	benign	-0.675	Destabilizing	0.835	D	0.387	neutral	D	0.559127204	None	None	N
L/N	0.9512	likely_pathogenic	0.9715	pathogenic	-2.497	Highly Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
L/P	0.9639	likely_pathogenic	0.9753	pathogenic	-1.122	Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
L/Q	0.6924	likely_pathogenic	0.7708	pathogenic	-2.164	Highly Destabilizing	0.996	D	0.854	deleterious	None	None	None	None	N
L/R	0.8027	likely_pathogenic	0.8599	pathogenic	-1.956	Destabilizing	0.996	D	0.853	deleterious	None	None	None	None	N
L/S	0.8494	likely_pathogenic	0.9101	pathogenic	-2.995	Highly Destabilizing	0.994	D	0.815	deleterious	D	0.638668452	None	None	N
L/T	0.7296	likely_pathogenic	0.8148	pathogenic	-2.536	Highly Destabilizing	0.996	D	0.752	deleterious	None	None	None	None	N
L/V	0.1827	likely_benign	0.2238	benign	-1.122	Destabilizing	0.835	D	0.537	neutral	D	0.57474281	None	None	N
L/W	0.4278	ambiguous	0.5213	ambiguous	-1.817	Destabilizing	1.0	D	0.836	deleterious	D	0.582948936	None	None	N
L/Y	0.6226	likely_pathogenic	0.7169	pathogenic	-1.516	Destabilizing	0.999	D	0.736	prob.delet.	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.