TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25481	76666;76667;76668	chr2:178569691;178569690;178569689	chr2:179434418;179434417;179434416
N2AB	23840	71743;71744;71745	chr2:178569691;178569690;178569689	chr2:179434418;179434417;179434416
N2A	22913	68962;68963;68964	chr2:178569691;178569690;178569689	chr2:179434418;179434417;179434416
N2B	16416	49471;49472;49473	chr2:178569691;178569690;178569689	chr2:179434418;179434417;179434416
Novex-1	16541	49846;49847;49848	chr2:178569691;178569690;178569689	chr2:179434418;179434417;179434416
Novex-2	16608	50047;50048;50049	chr2:178569691;178569690;178569689	chr2:179434418;179434417;179434416
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-73
• Domain position: 77
• Structural Position: 108
• Q(SASA): 0.0686
• 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	rs1324632548	None	0.002	N	0.211	0.056	0.232513804876	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs1324632548	None	0.002	N	0.211	0.056	0.232513804876	gnomAD-4.0.0	6.57419E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4708E-05	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	0.9415	likely_pathogenic	0.961	pathogenic	-3.042	Highly Destabilizing	0.559	D	0.614	neutral	None	None	None	None	N
I/C	0.9502	likely_pathogenic	0.9592	pathogenic	-2.583	Highly Destabilizing	0.998	D	0.731	prob.delet.	None	None	None	None	N
I/D	0.9988	likely_pathogenic	0.9991	pathogenic	-3.557	Highly Destabilizing	0.993	D	0.839	deleterious	None	None	None	None	N
I/E	0.9974	likely_pathogenic	0.9979	pathogenic	-3.313	Highly Destabilizing	0.978	D	0.819	deleterious	None	None	None	None	N
I/F	0.7458	likely_pathogenic	0.7832	pathogenic	-1.609	Destabilizing	0.942	D	0.639	neutral	N	0.514902037	None	None	N
I/G	0.9918	likely_pathogenic	0.9941	pathogenic	-3.51	Highly Destabilizing	0.978	D	0.793	deleterious	None	None	None	None	N
I/H	0.9962	likely_pathogenic	0.9969	pathogenic	-2.926	Highly Destabilizing	0.998	D	0.857	deleterious	None	None	None	None	N
I/K	0.9947	likely_pathogenic	0.9953	pathogenic	-2.511	Highly Destabilizing	0.978	D	0.822	deleterious	None	None	None	None	N
I/L	0.4114	ambiguous	0.4696	ambiguous	-1.621	Destabilizing	0.294	N	0.311	neutral	N	0.469864755	None	None	N
I/M	0.5497	ambiguous	0.6053	pathogenic	-1.883	Destabilizing	0.97	D	0.635	neutral	N	0.503799222	None	None	N
I/N	0.9819	likely_pathogenic	0.9857	pathogenic	-2.981	Highly Destabilizing	0.99	D	0.853	deleterious	N	0.515662506	None	None	N
I/P	0.9954	likely_pathogenic	0.9965	pathogenic	-2.09	Highly Destabilizing	0.993	D	0.841	deleterious	None	None	None	None	N
I/Q	0.9958	likely_pathogenic	0.9966	pathogenic	-2.758	Highly Destabilizing	0.993	D	0.858	deleterious	None	None	None	None	N
I/R	0.9915	likely_pathogenic	0.9926	pathogenic	-2.248	Highly Destabilizing	0.978	D	0.857	deleterious	None	None	None	None	N
I/S	0.9721	likely_pathogenic	0.9794	pathogenic	-3.513	Highly Destabilizing	0.97	D	0.759	deleterious	N	0.504306201	None	None	N
I/T	0.9313	likely_pathogenic	0.9527	pathogenic	-3.161	Highly Destabilizing	0.822	D	0.557	neutral	N	0.515409016	None	None	N
I/V	0.0844	likely_benign	0.0912	benign	-2.09	Highly Destabilizing	0.002	N	0.211	neutral	N	0.360751079	None	None	N
I/W	0.9969	likely_pathogenic	0.9972	pathogenic	-2.012	Highly Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	N
I/Y	0.9795	likely_pathogenic	0.9819	pathogenic	-1.967	Destabilizing	0.978	D	0.698	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.