TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25114	75565;75566;75567	chr2:178570792;178570791;178570790	chr2:179435519;179435518;179435517
N2AB	23473	70642;70643;70644	chr2:178570792;178570791;178570790	chr2:179435519;179435518;179435517
N2A	22546	67861;67862;67863	chr2:178570792;178570791;178570790	chr2:179435519;179435518;179435517
N2B	16049	48370;48371;48372	chr2:178570792;178570791;178570790	chr2:179435519;179435518;179435517
Novex-1	16174	48745;48746;48747	chr2:178570792;178570791;178570790	chr2:179435519;179435518;179435517
Novex-2	16241	48946;48947;48948	chr2:178570792;178570791;178570790	chr2:179435519;179435518;179435517
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: Ig-134
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4145
• 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
D/H	rs373701934	-0.703	1.0	D	0.721	0.41	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/H	rs373701934	-0.703	1.0	D	0.721	0.41	None	gnomAD-4.0.0	2.03007E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.40996E-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	0.3369	likely_benign	0.341	ambiguous	-0.369	Destabilizing	0.996	D	0.59	neutral	N	0.507977775	None	None	I
D/C	0.8265	likely_pathogenic	0.8429	pathogenic	-0.299	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
D/E	0.4032	ambiguous	0.4119	ambiguous	-0.439	Destabilizing	0.767	D	0.219	neutral	N	0.488770656	None	None	I
D/F	0.8056	likely_pathogenic	0.8096	pathogenic	-0.02	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
D/G	0.5313	ambiguous	0.5336	ambiguous	-0.622	Destabilizing	0.998	D	0.596	neutral	D	0.531450854	None	None	I
D/H	0.5047	ambiguous	0.5129	ambiguous	0.208	Stabilizing	1.0	D	0.721	prob.delet.	D	0.532211323	None	None	I
D/I	0.616	likely_pathogenic	0.638	pathogenic	0.269	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
D/K	0.7834	likely_pathogenic	0.7903	pathogenic	-0.04	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	I
D/L	0.5369	ambiguous	0.5409	ambiguous	0.269	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
D/M	0.8314	likely_pathogenic	0.8317	pathogenic	0.279	Stabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
D/N	0.2217	likely_benign	0.2264	benign	-0.485	Destabilizing	0.999	D	0.671	neutral	N	0.500633941	None	None	I
D/P	0.699	likely_pathogenic	0.7248	pathogenic	0.079	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	I
D/Q	0.7274	likely_pathogenic	0.7179	pathogenic	-0.399	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	I
D/R	0.831	likely_pathogenic	0.8278	pathogenic	0.319	Stabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	I
D/S	0.3032	likely_benign	0.3074	benign	-0.613	Destabilizing	0.997	D	0.603	neutral	None	None	None	None	I
D/T	0.6262	likely_pathogenic	0.634	pathogenic	-0.409	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
D/V	0.4238	ambiguous	0.4351	ambiguous	0.079	Stabilizing	0.999	D	0.721	prob.delet.	D	0.531450854	None	None	I
D/W	0.9586	likely_pathogenic	0.9585	pathogenic	0.172	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
D/Y	0.3373	likely_benign	0.3523	ambiguous	0.223	Stabilizing	1.0	D	0.762	deleterious	D	0.532464812	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.