TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32760	98503;98504;98505	chr2:178539787;178539786;178539785	chr2:179404514;179404513;179404512
N2AB	31119	93580;93581;93582	chr2:178539787;178539786;178539785	chr2:179404514;179404513;179404512
N2A	30192	90799;90800;90801	chr2:178539787;178539786;178539785	chr2:179404514;179404513;179404512
N2B	23695	71308;71309;71310	chr2:178539787;178539786;178539785	chr2:179404514;179404513;179404512
Novex-1	23820	71683;71684;71685	chr2:178539787;178539786;178539785	chr2:179404514;179404513;179404512
Novex-2	23887	71884;71885;71886	chr2:178539787;178539786;178539785	chr2:179404514;179404513;179404512
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-155
• Domain position: 53
• Structural Position: 138
• Q(SASA): 0.1204
• 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/F	rs1060500523	-1.744	1.0	N	0.797	0.511	0.758559352513	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.1489E-04	0	None	0	0	None	0	None	0	0	0
L/F	rs1060500523	-1.744	1.0	N	0.797	0.511	0.758559352513	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
L/F	rs1060500523	-1.744	1.0	N	0.797	0.511	0.758559352513	gnomAD-4.0.0	3.84332E-06	None	None	None	None	N	None	5.07528E-05	0	None	0	0	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	0.8877	likely_pathogenic	0.9091	pathogenic	-2.642	Highly Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
L/C	0.9044	likely_pathogenic	0.9119	pathogenic	-1.972	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9996	pathogenic	-3.518	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
L/E	0.9979	likely_pathogenic	0.9978	pathogenic	-3.202	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/F	0.6928	likely_pathogenic	0.6853	pathogenic	-1.648	Destabilizing	1.0	D	0.797	deleterious	N	0.499973421	None	None	N
L/G	0.9901	likely_pathogenic	0.9912	pathogenic	-3.249	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/H	0.9953	likely_pathogenic	0.9952	pathogenic	-2.959	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.555655765	None	None	N
L/I	0.2193	likely_benign	0.2162	benign	-0.825	Destabilizing	0.999	D	0.649	neutral	N	0.50801159	None	None	N
L/K	0.9962	likely_pathogenic	0.9957	pathogenic	-2.214	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/M	0.2827	likely_benign	0.2979	benign	-0.912	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
L/N	0.9976	likely_pathogenic	0.9974	pathogenic	-2.917	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
L/P	0.9991	likely_pathogenic	0.9989	pathogenic	-1.42	Destabilizing	1.0	D	0.894	deleterious	D	0.555655765	None	None	N
L/Q	0.9938	likely_pathogenic	0.9932	pathogenic	-2.589	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/R	0.9924	likely_pathogenic	0.9918	pathogenic	-2.224	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.555655765	None	None	N
L/S	0.9957	likely_pathogenic	0.9961	pathogenic	-3.486	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/T	0.9761	likely_pathogenic	0.9771	pathogenic	-3.0	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
L/V	0.2841	likely_benign	0.2864	benign	-1.42	Destabilizing	0.999	D	0.649	neutral	N	0.512899889	None	None	N
L/W	0.9763	likely_pathogenic	0.9761	pathogenic	-2.104	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/Y	0.9674	likely_pathogenic	0.9689	pathogenic	-1.819	Destabilizing	1.0	D	0.856	deleterious	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.