TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15932	48019;48020;48021	chr2:178617201;178617200;178617199	chr2:179481928;179481927;179481926
N2AB	14291	43096;43097;43098	chr2:178617201;178617200;178617199	chr2:179481928;179481927;179481926
N2A	13364	40315;40316;40317	chr2:178617201;178617200;178617199	chr2:179481928;179481927;179481926
N2B	6867	20824;20825;20826	chr2:178617201;178617200;178617199	chr2:179481928;179481927;179481926
Novex-1	6992	21199;21200;21201	chr2:178617201;178617200;178617199	chr2:179481928;179481927;179481926
Novex-2	7059	21400;21401;21402	chr2:178617201;178617200;178617199	chr2:179481928;179481927;179481926
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: Fn3-3
• Domain position: 74
• Structural Position: 106
• Q(SASA): 0.102
• 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/H	rs780464378	None	1.0	D	0.765	0.629	0.439870908748	gnomAD-4.0.0	4.25533E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.5963E-06	1.27756E-05	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
Y/A	0.9864	likely_pathogenic	0.9877	pathogenic	-2.777	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
Y/C	0.5997	likely_pathogenic	0.6785	pathogenic	-1.472	Destabilizing	1.0	D	0.859	deleterious	D	0.603500437	None	None	N
Y/D	0.9951	likely_pathogenic	0.9938	pathogenic	-3.607	Highly Destabilizing	1.0	D	0.865	deleterious	D	0.642239353	None	None	N
Y/E	0.9979	likely_pathogenic	0.9978	pathogenic	-3.381	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/F	0.0883	likely_benign	0.0865	benign	-1.213	Destabilizing	0.999	D	0.56	neutral	N	0.427450475	None	None	N
Y/G	0.9753	likely_pathogenic	0.9757	pathogenic	-3.189	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
Y/H	0.9436	likely_pathogenic	0.9369	pathogenic	-2.325	Highly Destabilizing	1.0	D	0.765	deleterious	D	0.579442492	None	None	N
Y/I	0.8028	likely_pathogenic	0.8172	pathogenic	-1.394	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
Y/K	0.9975	likely_pathogenic	0.9973	pathogenic	-2.458	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
Y/L	0.638	likely_pathogenic	0.6549	pathogenic	-1.394	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
Y/M	0.9191	likely_pathogenic	0.927	pathogenic	-1.049	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/N	0.98	likely_pathogenic	0.9774	pathogenic	-3.447	Highly Destabilizing	1.0	D	0.857	deleterious	D	0.642239353	None	None	N
Y/P	0.9949	likely_pathogenic	0.9937	pathogenic	-1.872	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/Q	0.9954	likely_pathogenic	0.9954	pathogenic	-3.046	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
Y/R	0.9918	likely_pathogenic	0.9909	pathogenic	-2.53	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
Y/S	0.9737	likely_pathogenic	0.9741	pathogenic	-3.605	Highly Destabilizing	1.0	D	0.849	deleterious	D	0.641720232	None	None	N
Y/T	0.9873	likely_pathogenic	0.9877	pathogenic	-3.249	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/V	0.7629	likely_pathogenic	0.7899	pathogenic	-1.872	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
Y/W	0.7	likely_pathogenic	0.6918	pathogenic	-0.636	Destabilizing	1.0	D	0.771	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.