TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9158	27697;27698;27699	chr2:178712450;178712449;178712448	chr2:179577177;179577176;179577175
N2AB	8841	26746;26747;26748	chr2:178712450;178712449;178712448	chr2:179577177;179577176;179577175
N2A	7914	23965;23966;23967	chr2:178712450;178712449;178712448	chr2:179577177;179577176;179577175
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-77
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1677
• 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/S	None	None	0.784	D	0.583	0.281	0.745366178539	gnomAD-4.0.0	1.59113E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85798E-06	0	0
C/Y	None	None	0.01	N	0.433	0.221	0.633466640759	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	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	0.5782	likely_pathogenic	0.5486	ambiguous	-1.692	Destabilizing	0.495	N	0.411	neutral	None	None	None	None	N
C/D	0.8945	likely_pathogenic	0.8825	pathogenic	-0.957	Destabilizing	0.981	D	0.68	prob.neutral	None	None	None	None	N
C/E	0.9043	likely_pathogenic	0.8923	pathogenic	-0.831	Destabilizing	0.981	D	0.684	prob.neutral	None	None	None	None	N
C/F	0.2208	likely_benign	0.2165	benign	-1.073	Destabilizing	0.006	N	0.435	neutral	N	0.464868895	None	None	N
C/G	0.3139	likely_benign	0.3031	benign	-2.015	Highly Destabilizing	0.917	D	0.634	neutral	D	0.532499397	None	None	N
C/H	0.6116	likely_pathogenic	0.5826	pathogenic	-2.216	Highly Destabilizing	0.893	D	0.671	neutral	None	None	None	None	N
C/I	0.4526	ambiguous	0.4218	ambiguous	-0.857	Destabilizing	0.329	N	0.568	neutral	None	None	None	None	N
C/K	0.8894	likely_pathogenic	0.8747	pathogenic	-1.282	Destabilizing	0.828	D	0.655	neutral	None	None	None	None	N
C/L	0.5017	ambiguous	0.477	ambiguous	-0.857	Destabilizing	0.003	N	0.348	neutral	None	None	None	None	N
C/M	0.631	likely_pathogenic	0.6073	pathogenic	0.11	Stabilizing	0.893	D	0.664	neutral	None	None	None	None	N
C/N	0.6811	likely_pathogenic	0.641	pathogenic	-1.358	Destabilizing	0.981	D	0.666	neutral	None	None	None	None	N
C/P	0.9881	likely_pathogenic	0.9826	pathogenic	-1.109	Destabilizing	0.981	D	0.665	neutral	None	None	None	None	N
C/Q	0.7551	likely_pathogenic	0.7379	pathogenic	-1.216	Destabilizing	0.981	D	0.673	neutral	None	None	None	None	N
C/R	0.6386	likely_pathogenic	0.6265	pathogenic	-1.246	Destabilizing	0.927	D	0.665	neutral	N	0.49388508	None	None	N
C/S	0.437	ambiguous	0.4065	ambiguous	-1.808	Destabilizing	0.784	D	0.583	neutral	D	0.526573502	None	None	N
C/T	0.5813	likely_pathogenic	0.5353	ambiguous	-1.504	Destabilizing	0.828	D	0.583	neutral	None	None	None	None	N
C/V	0.4374	ambiguous	0.4088	ambiguous	-1.109	Destabilizing	0.329	N	0.558	neutral	None	None	None	None	N
C/W	0.4808	ambiguous	0.457	ambiguous	-1.196	Destabilizing	0.975	D	0.632	neutral	N	0.491960207	None	None	N
C/Y	0.2606	likely_benign	0.2465	benign	-1.131	Destabilizing	0.01	N	0.433	neutral	N	0.397374467	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.