TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28683	86272;86273;86274	chr2:178560085;178560084;178560083	chr2:179424812;179424811;179424810
N2AB	27042	81349;81350;81351	chr2:178560085;178560084;178560083	chr2:179424812;179424811;179424810
N2A	26115	78568;78569;78570	chr2:178560085;178560084;178560083	chr2:179424812;179424811;179424810
N2B	19618	59077;59078;59079	chr2:178560085;178560084;178560083	chr2:179424812;179424811;179424810
Novex-1	19743	59452;59453;59454	chr2:178560085;178560084;178560083	chr2:179424812;179424811;179424810
Novex-2	19810	59653;59654;59655	chr2:178560085;178560084;178560083	chr2:179424812;179424811;179424810
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-97
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.194
• Predicted PPI site: I

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/T	rs1482174421	None	0.062	N	0.655	0.384	0.676853945565	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs1482174421	None	0.062	N	0.655	0.384	0.676853945565	gnomAD-4.0.0	6.57592E-06	None	None	None	None	I	None	2.41406E-05	0	None	0	0	None	0	0	0	0	0
I/V	rs1179601203	-1.599	None	N	0.136	0.195	0.185906805712	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.97E-06	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	0.8767	likely_pathogenic	0.8646	pathogenic	-2.096	Highly Destabilizing	0.035	N	0.491	neutral	None	None	None	None	I
I/C	0.9379	likely_pathogenic	0.928	pathogenic	-1.225	Destabilizing	0.824	D	0.686	prob.neutral	None	None	None	None	I
I/D	0.9938	likely_pathogenic	0.993	pathogenic	-1.803	Destabilizing	0.555	D	0.789	deleterious	None	None	None	None	I
I/E	0.9814	likely_pathogenic	0.9798	pathogenic	-1.749	Destabilizing	0.555	D	0.796	deleterious	None	None	None	None	I
I/F	0.8704	likely_pathogenic	0.8315	pathogenic	-1.436	Destabilizing	0.38	N	0.684	prob.neutral	None	None	None	None	I
I/G	0.9813	likely_pathogenic	0.9774	pathogenic	-2.485	Highly Destabilizing	0.262	N	0.797	deleterious	None	None	None	None	I
I/H	0.9889	likely_pathogenic	0.9866	pathogenic	-1.714	Destabilizing	0.935	D	0.757	deleterious	None	None	None	None	I
I/K	0.9785	likely_pathogenic	0.9755	pathogenic	-1.454	Destabilizing	0.484	N	0.799	deleterious	N	0.518539796	None	None	I
I/L	0.2926	likely_benign	0.3081	benign	-1.06	Destabilizing	0.005	N	0.345	neutral	N	0.508576813	None	None	I
I/M	0.4423	ambiguous	0.4327	ambiguous	-0.757	Destabilizing	0.317	N	0.675	prob.neutral	N	0.517525838	None	None	I
I/N	0.9172	likely_pathogenic	0.9111	pathogenic	-1.35	Destabilizing	0.791	D	0.791	deleterious	None	None	None	None	I
I/P	0.9184	likely_pathogenic	0.912	pathogenic	-1.378	Destabilizing	0.555	D	0.783	deleterious	None	None	None	None	I
I/Q	0.977	likely_pathogenic	0.9738	pathogenic	-1.493	Destabilizing	0.791	D	0.793	deleterious	None	None	None	None	I
I/R	0.9734	likely_pathogenic	0.9684	pathogenic	-0.856	Destabilizing	0.484	N	0.791	deleterious	D	0.529896102	None	None	I
I/S	0.9185	likely_pathogenic	0.9093	pathogenic	-2.004	Highly Destabilizing	0.149	N	0.765	deleterious	None	None	None	None	I
I/T	0.8356	likely_pathogenic	0.8234	pathogenic	-1.831	Destabilizing	0.062	N	0.655	neutral	N	0.494902133	None	None	I
I/V	0.0566	likely_benign	0.0535	benign	-1.378	Destabilizing	None	N	0.136	neutral	N	0.432828261	None	None	I
I/W	0.9973	likely_pathogenic	0.9964	pathogenic	-1.592	Destabilizing	0.935	D	0.764	deleterious	None	None	None	None	I
I/Y	0.981	likely_pathogenic	0.9745	pathogenic	-1.369	Destabilizing	0.555	D	0.717	prob.delet.	None	None	None	None	I

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.