TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27827	83704;83705;83706	chr2:178562653;178562652;178562651	chr2:179427380;179427379;179427378
N2AB	26186	78781;78782;78783	chr2:178562653;178562652;178562651	chr2:179427380;179427379;179427378
N2A	25259	76000;76001;76002	chr2:178562653;178562652;178562651	chr2:179427380;179427379;179427378
N2B	18762	56509;56510;56511	chr2:178562653;178562652;178562651	chr2:179427380;179427379;179427378
Novex-1	18887	56884;56885;56886	chr2:178562653;178562652;178562651	chr2:179427380;179427379;179427378
Novex-2	18954	57085;57086;57087	chr2:178562653;178562652;178562651	chr2:179427380;179427379;179427378
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: Fn3-90
• Domain position: 62
• Structural Position: 93
• Q(SASA): 0.0662
• 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/T	None	None	0.549	N	0.765	0.435	0.649176532554	gnomAD-4.0.0	1.62714E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.89631E-05	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
I/A	0.3026	likely_benign	0.2964	benign	-2.316	Highly Destabilizing	0.002	N	0.513	neutral	None	None	None	None	N
I/C	0.7443	likely_pathogenic	0.7408	pathogenic	-1.707	Destabilizing	0.977	D	0.807	deleterious	None	None	None	None	N
I/D	0.9738	likely_pathogenic	0.9775	pathogenic	-2.91	Highly Destabilizing	0.92	D	0.829	deleterious	None	None	None	None	N
I/E	0.938	likely_pathogenic	0.9423	pathogenic	-2.603	Highly Destabilizing	0.85	D	0.803	deleterious	None	None	None	None	N
I/F	0.3309	likely_benign	0.3311	benign	-1.437	Destabilizing	0.81	D	0.73	prob.delet.	N	0.487030731	None	None	N
I/G	0.8432	likely_pathogenic	0.8487	pathogenic	-2.906	Highly Destabilizing	0.447	N	0.789	deleterious	None	None	None	None	N
I/H	0.9264	likely_pathogenic	0.9347	pathogenic	-2.606	Highly Destabilizing	0.992	D	0.845	deleterious	None	None	None	None	N
I/K	0.9165	likely_pathogenic	0.9275	pathogenic	-1.829	Destabilizing	0.85	D	0.807	deleterious	None	None	None	None	N
I/L	0.1448	likely_benign	0.1383	benign	-0.563	Destabilizing	0.099	N	0.475	neutral	N	0.501333049	None	None	N
I/M	0.1154	likely_benign	0.1165	benign	-0.69	Destabilizing	0.81	D	0.658	neutral	N	0.513038705	None	None	N
I/N	0.8124	likely_pathogenic	0.8299	pathogenic	-2.454	Highly Destabilizing	0.896	D	0.844	deleterious	N	0.513545684	None	None	N
I/P	0.9081	likely_pathogenic	0.9213	pathogenic	-1.134	Destabilizing	0.92	D	0.835	deleterious	None	None	None	None	N
I/Q	0.9	likely_pathogenic	0.9041	pathogenic	-2.119	Highly Destabilizing	0.92	D	0.847	deleterious	None	None	None	None	N
I/R	0.8795	likely_pathogenic	0.8961	pathogenic	-1.942	Destabilizing	0.92	D	0.843	deleterious	None	None	None	None	N
I/S	0.5996	likely_pathogenic	0.6157	pathogenic	-3.07	Highly Destabilizing	0.379	N	0.782	deleterious	N	0.508265765	None	None	N
I/T	0.2664	likely_benign	0.2709	benign	-2.588	Highly Destabilizing	0.549	D	0.765	deleterious	N	0.493542099	None	None	N
I/V	0.0686	likely_benign	0.0657	benign	-1.134	Destabilizing	0.001	N	0.198	neutral	N	0.401555631	None	None	N
I/W	0.935	likely_pathogenic	0.9402	pathogenic	-1.818	Destabilizing	0.992	D	0.829	deleterious	None	None	None	None	N
I/Y	0.8324	likely_pathogenic	0.8483	pathogenic	-1.512	Destabilizing	0.92	D	0.814	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.