TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15701	47326;47327;47328	chr2:178618357;178618356;178618355	chr2:179483084;179483083;179483082
N2AB	14060	42403;42404;42405	chr2:178618357;178618356;178618355	chr2:179483084;179483083;179483082
N2A	13133	39622;39623;39624	chr2:178618357;178618356;178618355	chr2:179483084;179483083;179483082
N2B	6636	20131;20132;20133	chr2:178618357;178618356;178618355	chr2:179483084;179483083;179483082
Novex-1	6761	20506;20507;20508	chr2:178618357;178618356;178618355	chr2:179483084;179483083;179483082
Novex-2	6828	20707;20708;20709	chr2:178618357;178618356;178618355	chr2:179483084;179483083;179483082
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-1
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.3292
• 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
R/G	None	None	1.0	N	0.53	0.38	0.377799810692	gnomAD-4.0.0	1.59365E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43308E-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
R/A	0.9619	likely_pathogenic	0.9465	pathogenic	-0.244	Destabilizing	0.999	D	0.435	neutral	None	None	None	None	N
R/C	0.8921	likely_pathogenic	0.8135	pathogenic	-0.327	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
R/D	0.984	likely_pathogenic	0.9758	pathogenic	0.094	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	N
R/E	0.9292	likely_pathogenic	0.9054	pathogenic	0.181	Stabilizing	0.999	D	0.487	neutral	None	None	None	None	N
R/F	0.9818	likely_pathogenic	0.9713	pathogenic	-0.324	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
R/G	0.8725	likely_pathogenic	0.8353	pathogenic	-0.484	Destabilizing	1.0	D	0.53	neutral	N	0.474631433	None	None	N
R/H	0.6285	likely_pathogenic	0.5356	ambiguous	-0.833	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
R/I	0.9545	likely_pathogenic	0.945	pathogenic	0.367	Stabilizing	1.0	D	0.71	prob.delet.	D	0.545968389	None	None	N
R/K	0.4502	ambiguous	0.4014	ambiguous	-0.24	Destabilizing	0.997	D	0.402	neutral	N	0.467713941	None	None	N
R/L	0.8817	likely_pathogenic	0.8461	pathogenic	0.367	Stabilizing	1.0	D	0.53	neutral	None	None	None	None	N
R/M	0.9418	likely_pathogenic	0.9232	pathogenic	-0.04	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
R/N	0.9656	likely_pathogenic	0.9496	pathogenic	0.093	Stabilizing	1.0	D	0.609	neutral	None	None	None	None	N
R/P	0.9904	likely_pathogenic	0.9821	pathogenic	0.185	Stabilizing	1.0	D	0.627	neutral	None	None	None	None	N
R/Q	0.5854	likely_pathogenic	0.5009	ambiguous	-0.045	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
R/S	0.9718	likely_pathogenic	0.9605	pathogenic	-0.459	Destabilizing	1.0	D	0.566	neutral	N	0.46797898	None	None	N
R/T	0.9452	likely_pathogenic	0.9238	pathogenic	-0.216	Destabilizing	1.0	D	0.568	neutral	N	0.473025092	None	None	N
R/V	0.9597	likely_pathogenic	0.9517	pathogenic	0.185	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	N
R/W	0.8101	likely_pathogenic	0.7235	pathogenic	-0.222	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
R/Y	0.9399	likely_pathogenic	0.907	pathogenic	0.15	Stabilizing	1.0	D	0.666	neutral	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.