TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28245	84958;84959;84960	chr2:178561399;178561398;178561397	chr2:179426126;179426125;179426124
N2AB	26604	80035;80036;80037	chr2:178561399;178561398;178561397	chr2:179426126;179426125;179426124
N2A	25677	77254;77255;77256	chr2:178561399;178561398;178561397	chr2:179426126;179426125;179426124
N2B	19180	57763;57764;57765	chr2:178561399;178561398;178561397	chr2:179426126;179426125;179426124
Novex-1	19305	58138;58139;58140	chr2:178561399;178561398;178561397	chr2:179426126;179426125;179426124
Novex-2	19372	58339;58340;58341	chr2:178561399;178561398;178561397	chr2:179426126;179426125;179426124
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-93
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.7717
• Predicted PPI site: I

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
E/K	rs1481882166	None	0.191	N	0.552	0.209	0.239901079897	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
E/A	0.2138	likely_benign	0.1812	benign	-0.129	Destabilizing	0.321	N	0.497	neutral	N	0.518900089	None	None	I
E/C	0.8815	likely_pathogenic	0.8431	pathogenic	-0.142	Destabilizing	0.981	D	0.752	deleterious	None	None	None	None	I
E/D	0.0997	likely_benign	0.0894	benign	-0.27	Destabilizing	0.001	N	0.15	neutral	N	0.432763972	None	None	I
E/F	0.8075	likely_pathogenic	0.7456	pathogenic	-0.128	Destabilizing	0.931	D	0.673	prob.neutral	None	None	None	None	I
E/G	0.2598	likely_benign	0.2168	benign	-0.271	Destabilizing	0.321	N	0.533	neutral	N	0.466832426	None	None	I
E/H	0.592	likely_pathogenic	0.5237	ambiguous	0.394	Stabilizing	0.817	D	0.516	neutral	None	None	None	None	I
E/I	0.4098	ambiguous	0.3497	ambiguous	0.195	Stabilizing	0.817	D	0.689	prob.delet.	None	None	None	None	I
E/K	0.2386	likely_benign	0.204	benign	0.373	Stabilizing	0.191	N	0.552	neutral	N	0.518246728	None	None	I
E/L	0.4141	ambiguous	0.3572	ambiguous	0.195	Stabilizing	0.687	D	0.587	neutral	None	None	None	None	I
E/M	0.5159	ambiguous	0.4688	ambiguous	0.044	Stabilizing	0.981	D	0.7	prob.delet.	None	None	None	None	I
E/N	0.3072	likely_benign	0.254	benign	0.157	Stabilizing	0.239	N	0.517	neutral	None	None	None	None	I
E/P	0.4175	ambiguous	0.3435	ambiguous	0.106	Stabilizing	0.817	D	0.592	neutral	None	None	None	None	I
E/Q	0.1817	likely_benign	0.165	benign	0.165	Stabilizing	0.321	N	0.582	neutral	N	0.514128988	None	None	I
E/R	0.4003	ambiguous	0.3475	ambiguous	0.632	Stabilizing	0.002	N	0.284	neutral	None	None	None	None	I
E/S	0.2394	likely_benign	0.2031	benign	-0.013	Destabilizing	0.239	N	0.481	neutral	None	None	None	None	I
E/T	0.3073	likely_benign	0.2562	benign	0.105	Stabilizing	0.385	N	0.563	neutral	None	None	None	None	I
E/V	0.2715	likely_benign	0.2303	benign	0.106	Stabilizing	0.771	D	0.598	neutral	N	0.477477489	None	None	I
E/W	0.9368	likely_pathogenic	0.9132	pathogenic	-0.049	Destabilizing	0.981	D	0.785	deleterious	None	None	None	None	I
E/Y	0.6717	likely_pathogenic	0.609	pathogenic	0.105	Stabilizing	0.931	D	0.707	prob.delet.	None	None	None	None	I

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.