TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28130	84613;84614;84615	chr2:178561744;178561743;178561742	chr2:179426471;179426470;179426469
N2AB	26489	79690;79691;79692	chr2:178561744;178561743;178561742	chr2:179426471;179426470;179426469
N2A	25562	76909;76910;76911	chr2:178561744;178561743;178561742	chr2:179426471;179426470;179426469
N2B	19065	57418;57419;57420	chr2:178561744;178561743;178561742	chr2:179426471;179426470;179426469
Novex-1	19190	57793;57794;57795	chr2:178561744;178561743;178561742	chr2:179426471;179426470;179426469
Novex-2	19257	57994;57995;57996	chr2:178561744;178561743;178561742	chr2:179426471;179426470;179426469
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-92
• Domain position: 76
• Structural Position: 109
• Q(SASA): 0.0582
• 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
C/R	None	None	0.003	N	0.607	0.249	0.474010150167	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
C/W	None	None	0.987	N	0.717	0.309	0.464270400615	gnomAD-4.0.0	6.84538E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9976E-07	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
C/A	0.2915	likely_benign	0.2559	benign	-1.711	Destabilizing	0.002	N	0.191	neutral	None	None	None	None	N
C/D	0.9101	likely_pathogenic	0.8734	pathogenic	-1.82	Destabilizing	0.722	D	0.753	deleterious	None	None	None	None	N
C/E	0.9062	likely_pathogenic	0.8728	pathogenic	-1.583	Destabilizing	0.561	D	0.734	prob.delet.	None	None	None	None	N
C/F	0.2073	likely_benign	0.2005	benign	-1.164	Destabilizing	0.003	N	0.54	neutral	N	0.359634437	None	None	N
C/G	0.2079	likely_benign	0.1797	benign	-2.011	Highly Destabilizing	0.166	N	0.703	prob.neutral	N	0.451563163	None	None	N
C/H	0.5411	ambiguous	0.4861	ambiguous	-2.188	Highly Destabilizing	0.901	D	0.745	deleterious	None	None	None	None	N
C/I	0.6339	likely_pathogenic	0.602	pathogenic	-0.894	Destabilizing	0.39	N	0.707	prob.neutral	None	None	None	None	N
C/K	0.8428	likely_pathogenic	0.7903	pathogenic	-1.304	Destabilizing	0.39	N	0.722	prob.delet.	None	None	None	None	N
C/L	0.5306	ambiguous	0.4891	ambiguous	-0.894	Destabilizing	0.209	N	0.671	neutral	None	None	None	None	N
C/M	0.6296	likely_pathogenic	0.5765	pathogenic	-0.981	Destabilizing	0.901	D	0.725	prob.delet.	None	None	None	None	N
C/N	0.7139	likely_pathogenic	0.6397	pathogenic	-1.825	Destabilizing	0.561	D	0.754	deleterious	None	None	None	None	N
C/P	0.9964	likely_pathogenic	0.994	pathogenic	-1.149	Destabilizing	0.901	D	0.755	deleterious	None	None	None	None	N
C/Q	0.6413	likely_pathogenic	0.5954	pathogenic	-1.342	Destabilizing	0.818	D	0.756	deleterious	None	None	None	None	N
C/R	0.4924	ambiguous	0.4408	ambiguous	-1.74	Destabilizing	0.003	N	0.607	neutral	N	0.361229161	None	None	N
C/S	0.2515	likely_benign	0.2119	benign	-2.093	Highly Destabilizing	0.166	N	0.675	neutral	N	0.335584142	None	None	N
C/T	0.5437	ambiguous	0.4913	ambiguous	-1.705	Destabilizing	0.345	N	0.661	neutral	None	None	None	None	N
C/V	0.5414	ambiguous	0.502	ambiguous	-1.149	Destabilizing	0.345	N	0.669	neutral	None	None	None	None	N
C/W	0.5875	likely_pathogenic	0.5522	ambiguous	-1.627	Destabilizing	0.987	D	0.717	prob.delet.	N	0.495276655	None	None	N
C/Y	0.3047	likely_benign	0.2791	benign	-1.385	Destabilizing	0.013	N	0.529	neutral	N	0.398267396	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.