TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5800	17623;17624;17625	chr2:178731368;178731367;178731366	chr2:179596095;179596094;179596093
N2AB	5483	16672;16673;16674	chr2:178731368;178731367;178731366	chr2:179596095;179596094;179596093
N2A	4556	13891;13892;13893	chr2:178731368;178731367;178731366	chr2:179596095;179596094;179596093
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-41
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.0903
• 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
Y/C	rs1470486137	-0.962	1.0	D	0.877	0.894	0.789156113237	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
Y/H	None	None	1.0	D	0.781	0.868	0.654469489857	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
Y/N	None	None	1.0	D	0.885	0.881	0.846485612073	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	3.66327E-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
Y/A	0.9957	likely_pathogenic	0.9953	pathogenic	-2.422	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/C	0.9743	likely_pathogenic	0.9747	pathogenic	-1.346	Destabilizing	1.0	D	0.877	deleterious	D	0.618134369	None	None	N
Y/D	0.9985	likely_pathogenic	0.9982	pathogenic	-3.207	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.618134369	None	None	N
Y/E	0.9991	likely_pathogenic	0.9988	pathogenic	-2.958	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/F	0.1904	likely_benign	0.1991	benign	-0.911	Destabilizing	0.999	D	0.672	neutral	D	0.5838758	None	None	N
Y/G	0.9938	likely_pathogenic	0.993	pathogenic	-2.869	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/H	0.9886	likely_pathogenic	0.9872	pathogenic	-2.274	Highly Destabilizing	1.0	D	0.781	deleterious	D	0.617932564	None	None	N
Y/I	0.8776	likely_pathogenic	0.8632	pathogenic	-0.931	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/K	0.9992	likely_pathogenic	0.999	pathogenic	-1.958	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/L	0.8557	likely_pathogenic	0.8547	pathogenic	-0.931	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
Y/M	0.9673	likely_pathogenic	0.9694	pathogenic	-0.842	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/N	0.9906	likely_pathogenic	0.9895	pathogenic	-2.931	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.618134369	None	None	N
Y/P	0.9993	likely_pathogenic	0.9991	pathogenic	-1.445	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
Y/Q	0.9992	likely_pathogenic	0.999	pathogenic	-2.471	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/R	0.9974	likely_pathogenic	0.9966	pathogenic	-2.248	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/S	0.9952	likely_pathogenic	0.9948	pathogenic	-3.147	Highly Destabilizing	1.0	D	0.892	deleterious	D	0.618134369	None	None	N
Y/T	0.9958	likely_pathogenic	0.9954	pathogenic	-2.751	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/V	0.8533	likely_pathogenic	0.8512	pathogenic	-1.445	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
Y/W	0.8949	likely_pathogenic	0.8671	pathogenic	-0.302	Destabilizing	1.0	D	0.774	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.