TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19947	60064;60065;60066	chr2:178592065;178592064;178592063	chr2:179456792;179456791;179456790
N2AB	18306	55141;55142;55143	chr2:178592065;178592064;178592063	chr2:179456792;179456791;179456790
N2A	17379	52360;52361;52362	chr2:178592065;178592064;178592063	chr2:179456792;179456791;179456790
N2B	10882	32869;32870;32871	chr2:178592065;178592064;178592063	chr2:179456792;179456791;179456790
Novex-1	11007	33244;33245;33246	chr2:178592065;178592064;178592063	chr2:179456792;179456791;179456790
Novex-2	11074	33445;33446;33447	chr2:178592065;178592064;178592063	chr2:179456792;179456791;179456790
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-32
• Domain position: 71
• Structural Position: 104
• Q(SASA): 0.0811
• 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	rs1288648449	-2.615	0.999	D	0.792	0.849	0.830803960569	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
Y/H	rs1288648449	-2.615	0.999	D	0.792	0.849	0.830803960569	gnomAD-4.0.0	1.59292E-06	None	None	None	None	N	None	0	2.29032E-05	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
Y/A	0.9916	likely_pathogenic	0.993	pathogenic	-3.705	Highly Destabilizing	0.992	D	0.859	deleterious	None	None	None	None	N
Y/C	0.8888	likely_pathogenic	0.9098	pathogenic	-2.215	Highly Destabilizing	0.391	N	0.764	deleterious	D	0.672935895	None	None	N
Y/D	0.9885	likely_pathogenic	0.9937	pathogenic	-3.785	Highly Destabilizing	0.999	D	0.901	deleterious	D	0.672935895	None	None	N
Y/E	0.9968	likely_pathogenic	0.998	pathogenic	-3.613	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
Y/F	0.1735	likely_benign	0.1739	benign	-1.426	Destabilizing	0.998	D	0.735	prob.delet.	D	0.629562184	None	None	N
Y/G	0.985	likely_pathogenic	0.9892	pathogenic	-4.077	Highly Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
Y/H	0.9256	likely_pathogenic	0.9447	pathogenic	-2.46	Highly Destabilizing	0.999	D	0.792	deleterious	D	0.647397783	None	None	N
Y/I	0.904	likely_pathogenic	0.921	pathogenic	-2.451	Highly Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
Y/K	0.9969	likely_pathogenic	0.9983	pathogenic	-2.493	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
Y/L	0.9032	likely_pathogenic	0.8926	pathogenic	-2.451	Highly Destabilizing	0.992	D	0.807	deleterious	None	None	None	None	N
Y/M	0.9572	likely_pathogenic	0.9571	pathogenic	-2.155	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
Y/N	0.9339	likely_pathogenic	0.9549	pathogenic	-3.119	Highly Destabilizing	0.999	D	0.88	deleterious	D	0.67273409	None	None	N
Y/P	0.9987	likely_pathogenic	0.9993	pathogenic	-2.885	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
Y/Q	0.9937	likely_pathogenic	0.9953	pathogenic	-2.972	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/R	0.9923	likely_pathogenic	0.9952	pathogenic	-1.994	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/S	0.9736	likely_pathogenic	0.98	pathogenic	-3.497	Highly Destabilizing	0.998	D	0.86	deleterious	D	0.656916534	None	None	N
Y/T	0.9861	likely_pathogenic	0.9898	pathogenic	-3.223	Highly Destabilizing	0.999	D	0.87	deleterious	None	None	None	None	N
Y/V	0.859	likely_pathogenic	0.8791	pathogenic	-2.885	Highly Destabilizing	0.992	D	0.822	deleterious	None	None	None	None	N
Y/W	0.822	likely_pathogenic	0.8387	pathogenic	-0.711	Destabilizing	1.0	D	0.785	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.