TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27259	82000;82001;82002	chr2:178564357;178564356;178564355	chr2:179429084;179429083;179429082
N2AB	25618	77077;77078;77079	chr2:178564357;178564356;178564355	chr2:179429084;179429083;179429082
N2A	24691	74296;74297;74298	chr2:178564357;178564356;178564355	chr2:179429084;179429083;179429082
N2B	18194	54805;54806;54807	chr2:178564357;178564356;178564355	chr2:179429084;179429083;179429082
Novex-1	18319	55180;55181;55182	chr2:178564357;178564356;178564355	chr2:179429084;179429083;179429082
Novex-2	18386	55381;55382;55383	chr2:178564357;178564356;178564355	chr2:179429084;179429083;179429082
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: Fn3-86
• Domain position: 90
• Structural Position: 122
• Q(SASA): 0.5441
• 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/A	None	None	0.006	N	0.425	0.155	0.293502639404	gnomAD-4.0.0	6.84241E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99473E-07	0	0
D/G	rs1704865005	None	0.011	N	0.42	0.182	0.183819452728	gnomAD-4.0.0	6.84241E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15931E-05	0
D/V	None	None	0.026	N	0.568	0.157	0.461759001683	gnomAD-4.0.0	6.84241E-07	None	None	None	None	N	None	0	0	None	0	2.5227E-05	None	0	0	0	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	0.1056	likely_benign	0.0954	benign	-0.452	Destabilizing	0.006	N	0.425	neutral	N	0.475647957	None	None	N
D/C	0.5067	ambiguous	0.4673	ambiguous	0.109	Stabilizing	0.747	D	0.519	neutral	None	None	None	None	N
D/E	0.0563	likely_benign	0.0524	benign	-0.307	Destabilizing	None	N	0.119	neutral	N	0.370192574	None	None	N
D/F	0.4137	ambiguous	0.3653	ambiguous	-0.481	Destabilizing	0.439	N	0.526	neutral	None	None	None	None	N
D/G	0.1669	likely_benign	0.1372	benign	-0.62	Destabilizing	0.011	N	0.42	neutral	N	0.509531245	None	None	N
D/H	0.2676	likely_benign	0.2318	benign	-0.363	Destabilizing	0.162	N	0.463	neutral	N	0.472681777	None	None	N
D/I	0.1792	likely_benign	0.1569	benign	-0.058	Destabilizing	0.204	N	0.615	neutral	None	None	None	None	N
D/K	0.1872	likely_benign	0.1482	benign	0.387	Stabilizing	0.007	N	0.395	neutral	None	None	None	None	N
D/L	0.199	likely_benign	0.1753	benign	-0.058	Destabilizing	0.035	N	0.596	neutral	None	None	None	None	N
D/M	0.3512	ambiguous	0.3097	benign	0.22	Stabilizing	0.439	N	0.503	neutral	None	None	None	None	N
D/N	0.1229	likely_benign	0.1075	benign	0.097	Stabilizing	0.026	N	0.386	neutral	N	0.473090442	None	None	N
D/P	0.3502	ambiguous	0.3119	benign	-0.169	Destabilizing	None	N	0.295	neutral	None	None	None	None	N
D/Q	0.1761	likely_benign	0.1449	benign	0.1	Stabilizing	0.007	N	0.349	neutral	None	None	None	None	N
D/R	0.285	likely_benign	0.2335	benign	0.452	Stabilizing	0.018	N	0.61	neutral	None	None	None	None	N
D/S	0.1221	likely_benign	0.1096	benign	0.003	Stabilizing	0.007	N	0.382	neutral	None	None	None	None	N
D/T	0.1684	likely_benign	0.1488	benign	0.138	Stabilizing	0.015	N	0.427	neutral	None	None	None	None	N
D/V	0.1094	likely_benign	0.0984	benign	-0.169	Destabilizing	0.026	N	0.568	neutral	N	0.498140815	None	None	N
D/W	0.8044	likely_pathogenic	0.7588	pathogenic	-0.338	Destabilizing	0.747	D	0.553	neutral	None	None	None	None	N
D/Y	0.1993	likely_benign	0.1816	benign	-0.241	Destabilizing	0.371	N	0.542	neutral	N	0.505837578	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.