TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4988	15187;15188;15189	chr2:178734962;178734961;178734960	chr2:179599689;179599688;179599687
N2AB	4671	14236;14237;14238	chr2:178734962;178734961;178734960	chr2:179599689;179599688;179599687
N2A	3744	11455;11456;11457	chr2:178734962;178734961;178734960	chr2:179599689;179599688;179599687
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-33
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.3514
• 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
D/E	None	None	0.011	N	0.164	0.079	0.0401082797425	gnomAD-4.0.0	1.63507E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94125E-06	0	0
D/G	rs1029051488	None	0.896	N	0.474	0.232	0.124217242631	gnomAD-4.0.0	6.24316E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.27262E-06	0	1.67583E-05

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
D/A	0.2414	likely_benign	0.3149	benign	-0.38	Destabilizing	0.896	D	0.491	neutral	N	0.443401906	None	None	N
D/C	0.8443	likely_pathogenic	0.8973	pathogenic	-0.165	Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
D/E	0.1327	likely_benign	0.1844	benign	-0.278	Destabilizing	0.011	N	0.164	neutral	N	0.337163959	None	None	N
D/F	0.6457	likely_pathogenic	0.7285	pathogenic	0.005	Stabilizing	0.996	D	0.614	neutral	None	None	None	None	N
D/G	0.3283	likely_benign	0.4461	ambiguous	-0.637	Destabilizing	0.896	D	0.474	neutral	N	0.441829516	None	None	N
D/H	0.4872	ambiguous	0.6013	pathogenic	0.16	Stabilizing	0.984	D	0.529	neutral	N	0.442923682	None	None	N
D/I	0.4265	ambiguous	0.5257	ambiguous	0.271	Stabilizing	0.988	D	0.611	neutral	None	None	None	None	N
D/K	0.5782	likely_pathogenic	0.6975	pathogenic	0.147	Stabilizing	0.851	D	0.462	neutral	None	None	None	None	N
D/L	0.4305	ambiguous	0.5161	ambiguous	0.271	Stabilizing	0.976	D	0.59	neutral	None	None	None	None	N
D/M	0.6572	likely_pathogenic	0.75	pathogenic	0.363	Stabilizing	0.999	D	0.616	neutral	None	None	None	None	N
D/N	0.1712	likely_benign	0.2221	benign	-0.333	Destabilizing	0.103	N	0.233	neutral	N	0.433267329	None	None	N
D/P	0.5938	likely_pathogenic	0.7389	pathogenic	0.077	Stabilizing	0.988	D	0.534	neutral	None	None	None	None	N
D/Q	0.4487	ambiguous	0.5853	pathogenic	-0.239	Destabilizing	0.851	D	0.491	neutral	None	None	None	None	N
D/R	0.6545	likely_pathogenic	0.7524	pathogenic	0.433	Stabilizing	0.976	D	0.546	neutral	None	None	None	None	N
D/S	0.1808	likely_benign	0.2374	benign	-0.467	Destabilizing	0.919	D	0.493	neutral	None	None	None	None	N
D/T	0.355	ambiguous	0.4606	ambiguous	-0.253	Destabilizing	0.919	D	0.497	neutral	None	None	None	None	N
D/V	0.2801	likely_benign	0.3534	ambiguous	0.077	Stabilizing	0.984	D	0.591	neutral	N	0.434724487	None	None	N
D/W	0.9457	likely_pathogenic	0.9632	pathogenic	0.229	Stabilizing	0.999	D	0.671	neutral	None	None	None	None	N
D/Y	0.359	ambiguous	0.4312	ambiguous	0.265	Stabilizing	0.995	D	0.616	neutral	N	0.451946431	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.