TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22248	66967;66968;66969	chr2:178581526;178581525;178581524	chr2:179446253;179446252;179446251
N2AB	20607	62044;62045;62046	chr2:178581526;178581525;178581524	chr2:179446253;179446252;179446251
N2A	19680	59263;59264;59265	chr2:178581526;178581525;178581524	chr2:179446253;179446252;179446251
N2B	13183	39772;39773;39774	chr2:178581526;178581525;178581524	chr2:179446253;179446252;179446251
Novex-1	13308	40147;40148;40149	chr2:178581526;178581525;178581524	chr2:179446253;179446252;179446251
Novex-2	13375	40348;40349;40350	chr2:178581526;178581525;178581524	chr2:179446253;179446252;179446251
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: Fn3-49
• Domain position: 93
• Structural Position: 125
• Q(SASA): 0.7699
• 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/E	rs2047745662	None	None	N	0.124	0.102	0.107399877778	gnomAD-4.0.0	1.61291E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.05998E-05

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	0.1732	likely_benign	0.1656	benign	-0.221	Destabilizing	0.1	N	0.565	neutral	N	0.451590167	None	None	I
D/C	0.6358	likely_pathogenic	0.6038	pathogenic	-0.278	Destabilizing	0.96	D	0.757	deleterious	None	None	None	None	I
D/E	0.13	likely_benign	0.1214	benign	-0.054	Destabilizing	None	N	0.124	neutral	N	0.380132713	None	None	I
D/F	0.7129	likely_pathogenic	0.689	pathogenic	-0.262	Destabilizing	0.864	D	0.743	deleterious	None	None	None	None	I
D/G	0.1289	likely_benign	0.1216	benign	-0.364	Destabilizing	None	N	0.307	neutral	N	0.376169688	None	None	I
D/H	0.4065	ambiguous	0.3982	ambiguous	0.179	Stabilizing	0.856	D	0.531	neutral	D	0.527589435	None	None	I
D/I	0.504	ambiguous	0.4738	ambiguous	0.104	Stabilizing	0.676	D	0.745	deleterious	None	None	None	None	I
D/K	0.4629	ambiguous	0.4329	ambiguous	-0.028	Destabilizing	0.128	N	0.537	neutral	None	None	None	None	I
D/L	0.426	ambiguous	0.4049	ambiguous	0.104	Stabilizing	0.507	D	0.657	prob.neutral	None	None	None	None	I
D/M	0.673	likely_pathogenic	0.6297	pathogenic	-0.058	Destabilizing	0.96	D	0.713	prob.delet.	None	None	None	None	I
D/N	0.1455	likely_benign	0.136	benign	0.014	Stabilizing	0.181	N	0.559	neutral	N	0.443837475	None	None	I
D/P	0.738	likely_pathogenic	0.7373	pathogenic	0.015	Stabilizing	0.676	D	0.551	neutral	None	None	None	None	I
D/Q	0.3289	likely_benign	0.3196	benign	0.021	Stabilizing	0.34	N	0.453	neutral	None	None	None	None	I
D/R	0.5287	ambiguous	0.515	ambiguous	0.273	Stabilizing	0.507	D	0.699	prob.delet.	None	None	None	None	I
D/S	0.1522	likely_benign	0.1445	benign	-0.208	Destabilizing	0.128	N	0.452	neutral	None	None	None	None	I
D/T	0.2982	likely_benign	0.2754	benign	-0.105	Destabilizing	0.227	N	0.564	neutral	None	None	None	None	I
D/V	0.2867	likely_benign	0.2728	benign	0.015	Stabilizing	0.437	N	0.617	neutral	N	0.483529227	None	None	I
D/W	0.9196	likely_pathogenic	0.9114	pathogenic	-0.202	Destabilizing	0.96	D	0.781	deleterious	None	None	None	None	I
D/Y	0.3521	ambiguous	0.3492	ambiguous	-0.06	Destabilizing	0.828	D	0.735	deleterious	D	0.527589435	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.