TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28320	85183;85184;85185	chr2:178561174;178561173;178561172	chr2:179425901;179425900;179425899
N2AB	26679	80260;80261;80262	chr2:178561174;178561173;178561172	chr2:179425901;179425900;179425899
N2A	25752	77479;77480;77481	chr2:178561174;178561173;178561172	chr2:179425901;179425900;179425899
N2B	19255	57988;57989;57990	chr2:178561174;178561173;178561172	chr2:179425901;179425900;179425899
Novex-1	19380	58363;58364;58365	chr2:178561174;178561173;178561172	chr2:179425901;179425900;179425899
Novex-2	19447	58564;58565;58566	chr2:178561174;178561173;178561172	chr2:179425901;179425900;179425899
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: Fn3-94
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.8332
• 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/N	rs767491713	-0.44	0.988	N	0.772	0.291	0.18274738541	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	8.91E-06	0
D/N	rs767491713	-0.44	0.988	N	0.772	0.291	0.18274738541	gnomAD-4.0.0	5.47424E-06	None	None	None	None	N	None	0	2.23644E-05	None	0	0	None	0	0	6.29616E-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	0.3629	ambiguous	0.3507	ambiguous	-0.396	Destabilizing	0.919	D	0.697	prob.neutral	N	0.504416213	None	None	N
D/C	0.7859	likely_pathogenic	0.7827	pathogenic	-0.189	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
D/E	0.2532	likely_benign	0.2559	benign	-0.472	Destabilizing	0.979	D	0.547	neutral	N	0.484483658	None	None	N
D/F	0.68	likely_pathogenic	0.6773	pathogenic	-0.191	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
D/G	0.1344	likely_benign	0.133	benign	-0.647	Destabilizing	0.067	N	0.469	neutral	N	0.390546416	None	None	N
D/H	0.4319	ambiguous	0.4176	ambiguous	-0.19	Destabilizing	0.999	D	0.753	deleterious	N	0.469140285	None	None	N
D/I	0.7404	likely_pathogenic	0.7127	pathogenic	0.234	Stabilizing	0.998	D	0.811	deleterious	None	None	None	None	N
D/K	0.6083	likely_pathogenic	0.5707	pathogenic	-0.074	Destabilizing	0.991	D	0.762	deleterious	None	None	None	None	N
D/L	0.5761	likely_pathogenic	0.5573	ambiguous	0.234	Stabilizing	0.995	D	0.785	deleterious	None	None	None	None	N
D/M	0.7621	likely_pathogenic	0.7508	pathogenic	0.378	Stabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
D/N	0.0933	likely_benign	0.0984	benign	-0.37	Destabilizing	0.988	D	0.772	deleterious	N	0.434670914	None	None	N
D/P	0.9535	likely_pathogenic	0.9398	pathogenic	0.047	Stabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
D/Q	0.5237	ambiguous	0.5111	ambiguous	-0.321	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
D/R	0.647	likely_pathogenic	0.6169	pathogenic	0.17	Stabilizing	0.995	D	0.813	deleterious	None	None	None	None	N
D/S	0.2018	likely_benign	0.2024	benign	-0.535	Destabilizing	0.968	D	0.753	deleterious	None	None	None	None	N
D/T	0.4766	ambiguous	0.4768	ambiguous	-0.345	Destabilizing	0.995	D	0.765	deleterious	None	None	None	None	N
D/V	0.566	likely_pathogenic	0.537	ambiguous	0.047	Stabilizing	0.994	D	0.785	deleterious	N	0.487866878	None	None	N
D/W	0.9183	likely_pathogenic	0.9086	pathogenic	-0.034	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
D/Y	0.276	likely_benign	0.259	benign	0.038	Stabilizing	0.999	D	0.807	deleterious	N	0.517518797	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.