TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5703	17332;17333;17334	chr2:178731768;178731767;178731766	chr2:179596495;179596494;179596493
N2AB	5386	16381;16382;16383	chr2:178731768;178731767;178731766	chr2:179596495;179596494;179596493
N2A	4459	13600;13601;13602	chr2:178731768;178731767;178731766	chr2:179596495;179596494;179596493
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-40
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1293
• 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/V	None	None	1.0	D	0.887	0.863	0.918775219941	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	0.8766	likely_pathogenic	0.8409	pathogenic	1.934	Stabilizing	1.0	D	0.875	deleterious	D	0.619495201	None	None	N
D/C	0.9759	likely_pathogenic	0.9672	pathogenic	1.468	Stabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
D/E	0.7514	likely_pathogenic	0.6889	pathogenic	-0.068	Destabilizing	1.0	D	0.581	neutral	D	0.59855038	None	None	N
D/F	0.9881	likely_pathogenic	0.9862	pathogenic	2.386	Highly Stabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
D/G	0.9225	likely_pathogenic	0.8961	pathogenic	1.462	Stabilizing	1.0	D	0.823	deleterious	D	0.645002953	None	None	N
D/H	0.9206	likely_pathogenic	0.9102	pathogenic	2.059	Highly Stabilizing	1.0	D	0.885	deleterious	D	0.587627923	None	None	N
D/I	0.9791	likely_pathogenic	0.9749	pathogenic	3.179	Highly Stabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
D/K	0.982	likely_pathogenic	0.9753	pathogenic	1.553	Stabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
D/L	0.9756	likely_pathogenic	0.9709	pathogenic	3.179	Highly Stabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
D/M	0.9858	likely_pathogenic	0.9825	pathogenic	3.24	Highly Stabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
D/N	0.7145	likely_pathogenic	0.6576	pathogenic	0.598	Stabilizing	1.0	D	0.805	deleterious	D	0.601629242	None	None	N
D/P	0.9955	likely_pathogenic	0.9946	pathogenic	2.798	Highly Stabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
D/Q	0.9554	likely_pathogenic	0.9414	pathogenic	1.04	Stabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
D/R	0.9846	likely_pathogenic	0.9801	pathogenic	1.197	Stabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
D/S	0.8079	likely_pathogenic	0.7531	pathogenic	0.392	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
D/T	0.9494	likely_pathogenic	0.9328	pathogenic	0.855	Stabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
D/V	0.9375	likely_pathogenic	0.9229	pathogenic	2.798	Highly Stabilizing	1.0	D	0.887	deleterious	D	0.645406561	None	None	N
D/W	0.9978	likely_pathogenic	0.9972	pathogenic	2.119	Highly Stabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
D/Y	0.9299	likely_pathogenic	0.9087	pathogenic	2.672	Highly Stabilizing	1.0	D	0.899	deleterious	D	0.629185396	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.