TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21158	63697;63698;63699	chr2:178587935;178587934;178587933	chr2:179452662;179452661;179452660
N2AB	19517	58774;58775;58776	chr2:178587935;178587934;178587933	chr2:179452662;179452661;179452660
N2A	18590	55993;55994;55995	chr2:178587935;178587934;178587933	chr2:179452662;179452661;179452660
N2B	12093	36502;36503;36504	chr2:178587935;178587934;178587933	chr2:179452662;179452661;179452660
Novex-1	12218	36877;36878;36879	chr2:178587935;178587934;178587933	chr2:179452662;179452661;179452660
Novex-2	12285	37078;37079;37080	chr2:178587935;178587934;178587933	chr2:179452662;179452661;179452660
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-41
• Domain position: 95
• Structural Position: 122
• Q(SASA): 0.3922
• 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
E/K	None	None	0.842	N	0.503	0.19	0.251116650651	gnomAD-4.0.0	1.37511E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02757E-07	1.16995E-05	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	0.1302	likely_benign	0.1245	benign	-0.188	Destabilizing	0.915	D	0.573	neutral	N	0.434718481	None	None	N
E/C	0.6932	likely_pathogenic	0.687	pathogenic	-0.165	Destabilizing	0.998	D	0.721	deleterious	None	None	None	None	N
E/D	0.1554	likely_benign	0.1523	benign	-0.93	Destabilizing	0.016	N	0.257	neutral	N	0.412033622	None	None	N
E/F	0.5058	ambiguous	0.5006	ambiguous	0.777	Stabilizing	0.925	D	0.659	prob.neutral	None	None	None	None	N
E/G	0.2007	likely_benign	0.1918	benign	-0.602	Destabilizing	0.842	D	0.593	neutral	N	0.44797578	None	None	N
E/H	0.3619	ambiguous	0.3561	ambiguous	0.747	Stabilizing	0.961	D	0.55	neutral	None	None	None	None	N
E/I	0.2033	likely_benign	0.1947	benign	0.953	Stabilizing	0.981	D	0.685	prob.delet.	None	None	None	None	N
E/K	0.1679	likely_benign	0.1598	benign	-0.023	Destabilizing	0.842	D	0.503	neutral	N	0.449071858	None	None	N
E/L	0.2349	likely_benign	0.2271	benign	0.953	Stabilizing	0.876	D	0.607	neutral	None	None	None	None	N
E/M	0.291	likely_benign	0.285	benign	1.13	Stabilizing	0.998	D	0.663	prob.neutral	None	None	None	None	N
E/N	0.2406	likely_benign	0.2333	benign	-0.796	Destabilizing	0.087	N	0.334	neutral	None	None	None	None	N
E/P	0.4098	ambiguous	0.3915	ambiguous	0.595	Stabilizing	0.994	D	0.636	neutral	None	None	None	None	N
E/Q	0.1285	likely_benign	0.1258	benign	-0.58	Destabilizing	0.915	D	0.545	neutral	N	0.450226651	None	None	N
E/R	0.2605	likely_benign	0.2473	benign	0.335	Stabilizing	0.981	D	0.545	neutral	None	None	None	None	N
E/S	0.1805	likely_benign	0.1761	benign	-1.112	Destabilizing	0.876	D	0.506	neutral	None	None	None	None	N
E/T	0.1625	likely_benign	0.1567	benign	-0.737	Destabilizing	0.876	D	0.569	neutral	None	None	None	None	N
E/V	0.1253	likely_benign	0.1187	benign	0.595	Stabilizing	0.842	D	0.578	neutral	N	0.467254974	None	None	N
E/W	0.7976	likely_pathogenic	0.79	pathogenic	1.058	Stabilizing	0.998	D	0.693	prob.delet.	None	None	None	None	N
E/Y	0.4465	ambiguous	0.4365	ambiguous	1.096	Stabilizing	0.087	N	0.434	neutral	None	None	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.