TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31328	94207;94208;94209	chr2:178547644;178547643;178547642	chr2:179412371;179412370;179412369
N2AB	29687	89284;89285;89286	chr2:178547644;178547643;178547642	chr2:179412371;179412370;179412369
N2A	28760	86503;86504;86505	chr2:178547644;178547643;178547642	chr2:179412371;179412370;179412369
N2B	22263	67012;67013;67014	chr2:178547644;178547643;178547642	chr2:179412371;179412370;179412369
Novex-1	22388	67387;67388;67389	chr2:178547644;178547643;178547642	chr2:179412371;179412370;179412369
Novex-2	22455	67588;67589;67590	chr2:178547644;178547643;178547642	chr2:179412371;179412370;179412369
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: Fn3-116
• Domain position: 21
• Structural Position: 22
• Q(SASA): 0.1404
• 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/R	rs754710293	-1.744	1.0	D	0.837	0.797	0.830618923432	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
L/R	rs754710293	-1.744	1.0	D	0.837	0.797	0.830618923432	gnomAD-4.0.0	1.59107E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85799E-06	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	0.9567	likely_pathogenic	0.9353	pathogenic	-2.395	Highly Destabilizing	0.999	D	0.64	neutral	None	None	None	None	N
L/C	0.8834	likely_pathogenic	0.8513	pathogenic	-1.574	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9996	pathogenic	-3.035	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/E	0.9984	likely_pathogenic	0.9974	pathogenic	-2.706	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/F	0.376	ambiguous	0.4494	ambiguous	-1.425	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
L/G	0.9954	likely_pathogenic	0.9922	pathogenic	-3.021	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/H	0.9944	likely_pathogenic	0.992	pathogenic	-2.83	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/I	0.1132	likely_benign	0.1113	benign	-0.529	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	N
L/K	0.997	likely_pathogenic	0.9956	pathogenic	-1.821	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
L/M	0.2773	likely_benign	0.2806	benign	-0.649	Destabilizing	1.0	D	0.675	neutral	N	0.49736503	None	None	N
L/N	0.9987	likely_pathogenic	0.9976	pathogenic	-2.527	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/P	0.9974	likely_pathogenic	0.9951	pathogenic	-1.139	Destabilizing	1.0	D	0.885	deleterious	D	0.543715305	None	None	N
L/Q	0.9927	likely_pathogenic	0.9889	pathogenic	-2.144	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.543715305	None	None	N
L/R	0.9927	likely_pathogenic	0.9903	pathogenic	-1.966	Destabilizing	1.0	D	0.837	deleterious	D	0.543715305	None	None	N
L/S	0.9958	likely_pathogenic	0.993	pathogenic	-3.107	Highly Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
L/T	0.9814	likely_pathogenic	0.9663	pathogenic	-2.604	Highly Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
L/V	0.1746	likely_benign	0.1566	benign	-1.139	Destabilizing	0.999	D	0.558	neutral	N	0.498263819	None	None	N
L/W	0.9655	likely_pathogenic	0.9649	pathogenic	-1.881	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
L/Y	0.9669	likely_pathogenic	0.9626	pathogenic	-1.568	Destabilizing	1.0	D	0.724	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.