TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21992	66199;66200;66201	chr2:178582482;178582481;178582480	chr2:179447209;179447208;179447207
N2AB	20351	61276;61277;61278	chr2:178582482;178582481;178582480	chr2:179447209;179447208;179447207
N2A	19424	58495;58496;58497	chr2:178582482;178582481;178582480	chr2:179447209;179447208;179447207
N2B	12927	39004;39005;39006	chr2:178582482;178582481;178582480	chr2:179447209;179447208;179447207
Novex-1	13052	39379;39380;39381	chr2:178582482;178582481;178582480	chr2:179447209;179447208;179447207
Novex-2	13119	39580;39581;39582	chr2:178582482;178582481;178582480	chr2:179447209;179447208;179447207
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-47
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1819
• 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
I/V	None	None	0.02	N	0.249	0.077	0.371157983038	gnomAD-4.0.0	1.59321E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86151E-06	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
I/A	0.7446	likely_pathogenic	0.6597	pathogenic	-2.363	Highly Destabilizing	0.91	D	0.631	neutral	None	None	None	None	N
I/C	0.8748	likely_pathogenic	0.8151	pathogenic	-1.822	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
I/D	0.9868	likely_pathogenic	0.9771	pathogenic	-2.924	Highly Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
I/E	0.9286	likely_pathogenic	0.911	pathogenic	-2.85	Highly Destabilizing	0.993	D	0.738	prob.delet.	None	None	None	None	N
I/F	0.5962	likely_pathogenic	0.4467	ambiguous	-1.611	Destabilizing	0.991	D	0.692	prob.neutral	N	0.517364081	None	None	N
I/G	0.9691	likely_pathogenic	0.9547	pathogenic	-2.754	Highly Destabilizing	0.993	D	0.738	prob.delet.	None	None	None	None	N
I/H	0.8644	likely_pathogenic	0.7892	pathogenic	-1.965	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
I/K	0.6974	likely_pathogenic	0.6669	pathogenic	-1.825	Destabilizing	0.993	D	0.741	deleterious	None	None	None	None	N
I/L	0.3262	likely_benign	0.2818	benign	-1.292	Destabilizing	0.58	D	0.425	neutral	N	0.511379471	None	None	N
I/M	0.286	likely_benign	0.2309	benign	-1.146	Destabilizing	0.991	D	0.699	prob.neutral	N	0.489966792	None	None	N
I/N	0.8376	likely_pathogenic	0.7565	pathogenic	-1.911	Destabilizing	0.997	D	0.783	deleterious	N	0.467188048	None	None	N
I/P	0.9971	likely_pathogenic	0.9949	pathogenic	-1.625	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
I/Q	0.8144	likely_pathogenic	0.763	pathogenic	-2.056	Highly Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
I/R	0.577	likely_pathogenic	0.5241	ambiguous	-1.19	Destabilizing	0.998	D	0.782	deleterious	None	None	None	None	N
I/S	0.7485	likely_pathogenic	0.6593	pathogenic	-2.473	Highly Destabilizing	0.991	D	0.668	neutral	N	0.506933657	None	None	N
I/T	0.2946	likely_benign	0.2323	benign	-2.287	Highly Destabilizing	0.939	D	0.663	neutral	N	0.449618936	None	None	N
I/V	0.0696	likely_benign	0.0742	benign	-1.625	Destabilizing	0.02	N	0.249	neutral	N	0.428494303	None	None	N
I/W	0.9593	likely_pathogenic	0.9152	pathogenic	-1.842	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
I/Y	0.8974	likely_pathogenic	0.8093	pathogenic	-1.633	Destabilizing	0.998	D	0.705	prob.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.