TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17928	54007;54008;54009	chr2:178605513;178605512;178605511	chr2:179470240;179470239;179470238
N2AB	16287	49084;49085;49086	chr2:178605513;178605512;178605511	chr2:179470240;179470239;179470238
N2A	15360	46303;46304;46305	chr2:178605513;178605512;178605511	chr2:179470240;179470239;179470238
N2B	8863	26812;26813;26814	chr2:178605513;178605512;178605511	chr2:179470240;179470239;179470238
Novex-1	8988	27187;27188;27189	chr2:178605513;178605512;178605511	chr2:179470240;179470239;179470238
Novex-2	9055	27388;27389;27390	chr2:178605513;178605512;178605511	chr2:179470240;179470239;179470238
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: Fn3-18
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.2184
• 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/G	None	None	0.669	N	0.355	0.221	0.219573609325	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

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	0.1182	likely_benign	0.1003	benign	-0.222	Destabilizing	0.012	N	0.251	neutral	N	0.439364657	None	None	N
D/C	0.6024	likely_pathogenic	0.533	ambiguous	-0.068	Destabilizing	0.993	D	0.507	neutral	None	None	None	None	N
D/E	0.1136	likely_benign	0.0963	benign	-0.535	Destabilizing	0.051	N	0.133	neutral	N	0.403961217	None	None	N
D/F	0.5687	likely_pathogenic	0.5136	ambiguous	0.431	Stabilizing	0.974	D	0.484	neutral	None	None	None	None	N
D/G	0.1926	likely_benign	0.1795	benign	-0.595	Destabilizing	0.669	D	0.355	neutral	N	0.515825286	None	None	N
D/H	0.2706	likely_benign	0.2252	benign	0.332	Stabilizing	0.966	D	0.399	neutral	N	0.452525956	None	None	N
D/I	0.2893	likely_benign	0.209	benign	0.761	Stabilizing	0.949	D	0.488	neutral	None	None	None	None	N
D/K	0.2986	likely_benign	0.2538	benign	0.111	Stabilizing	0.728	D	0.353	neutral	None	None	None	None	N
D/L	0.2621	likely_benign	0.2209	benign	0.761	Stabilizing	0.842	D	0.421	neutral	None	None	None	None	N
D/M	0.4643	ambiguous	0.3964	ambiguous	0.99	Stabilizing	0.998	D	0.477	neutral	None	None	None	None	N
D/N	0.1262	likely_benign	0.1098	benign	-0.599	Destabilizing	0.891	D	0.421	neutral	N	0.438903297	None	None	N
D/P	0.5064	ambiguous	0.5088	ambiguous	0.46	Stabilizing	0.974	D	0.349	neutral	None	None	None	None	N
D/Q	0.241	likely_benign	0.2057	benign	-0.413	Destabilizing	0.325	N	0.238	neutral	None	None	None	None	N
D/R	0.3579	ambiguous	0.3163	benign	0.357	Stabilizing	0.949	D	0.397	neutral	None	None	None	None	N
D/S	0.1178	likely_benign	0.0996	benign	-0.786	Destabilizing	0.728	D	0.352	neutral	None	None	None	None	N
D/T	0.182	likely_benign	0.141	benign	-0.461	Destabilizing	0.842	D	0.375	neutral	None	None	None	None	N
D/V	0.1609	likely_benign	0.1196	benign	0.46	Stabilizing	0.669	D	0.409	neutral	N	0.436575068	None	None	N
D/W	0.8461	likely_pathogenic	0.8186	pathogenic	0.671	Stabilizing	0.998	D	0.577	neutral	None	None	None	None	N
D/Y	0.287	likely_benign	0.257	benign	0.726	Stabilizing	0.989	D	0.486	neutral	N	0.486465171	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.