TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22266	67021;67022;67023	chr2:178580583;178580582;178580581	chr2:179445310;179445309;179445308
N2AB	20625	62098;62099;62100	chr2:178580583;178580582;178580581	chr2:179445310;179445309;179445308
N2A	19698	59317;59318;59319	chr2:178580583;178580582;178580581	chr2:179445310;179445309;179445308
N2B	13201	39826;39827;39828	chr2:178580583;178580582;178580581	chr2:179445310;179445309;179445308
Novex-1	13326	40201;40202;40203	chr2:178580583;178580582;178580581	chr2:179445310;179445309;179445308
Novex-2	13393	40402;40403;40404	chr2:178580583;178580582;178580581	chr2:179445310;179445309;179445308
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-126
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.7208
• 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	rs1380514691	0.069	None	N	0.255	0.048	0.0762999501168	gnomAD-2.1.1	4.08E-06	None	None	None	None	I	None	6.51E-05	0	None	0	0	None	0	None	0	0	0
D/E	rs1380514691	0.069	None	N	0.255	0.048	0.0762999501168	gnomAD-4.0.0	6.8535E-07	None	None	None	None	I	None	2.99814E-05	0	None	0	0	None	0	0	0	0	0
D/N	None	None	0.22	D	0.447	0.196	0.298745278005	gnomAD-4.0.0	1.59782E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86518E-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	0.2682	likely_benign	0.3352	benign	-0.084	Destabilizing	0.124	N	0.471	neutral	D	0.530685669	None	None	I
D/C	0.8259	likely_pathogenic	0.8697	pathogenic	-0.078	Destabilizing	0.968	D	0.565	neutral	None	None	None	None	I
D/E	0.1114	likely_benign	0.148	benign	-0.184	Destabilizing	None	N	0.255	neutral	N	0.459265501	None	None	I
D/F	0.81	likely_pathogenic	0.8566	pathogenic	0.038	Stabilizing	0.726	D	0.516	neutral	None	None	None	None	I
D/G	0.3449	ambiguous	0.4298	ambiguous	-0.262	Destabilizing	0.124	N	0.408	neutral	N	0.493687592	None	None	I
D/H	0.5498	ambiguous	0.6338	pathogenic	0.421	Stabilizing	0.667	D	0.373	neutral	D	0.523567695	None	None	I
D/I	0.5571	ambiguous	0.6555	pathogenic	0.33	Stabilizing	0.726	D	0.509	neutral	None	None	None	None	I
D/K	0.5776	likely_pathogenic	0.7051	pathogenic	0.436	Stabilizing	0.157	N	0.404	neutral	None	None	None	None	I
D/L	0.5515	ambiguous	0.6449	pathogenic	0.33	Stabilizing	0.567	D	0.503	neutral	None	None	None	None	I
D/M	0.7431	likely_pathogenic	0.8015	pathogenic	0.231	Stabilizing	0.968	D	0.529	neutral	None	None	None	None	I
D/N	0.1842	likely_benign	0.2304	benign	0.049	Stabilizing	0.22	N	0.447	neutral	D	0.523220979	None	None	I
D/P	0.8707	likely_pathogenic	0.886	pathogenic	0.214	Stabilizing	0.726	D	0.359	neutral	None	None	None	None	I
D/Q	0.4787	ambiguous	0.5652	pathogenic	0.103	Stabilizing	0.396	N	0.353	neutral	None	None	None	None	I
D/R	0.6864	likely_pathogenic	0.7658	pathogenic	0.664	Stabilizing	0.396	N	0.48	neutral	None	None	None	None	I
D/S	0.1876	likely_benign	0.2454	benign	-0.035	Destabilizing	0.005	N	0.33	neutral	None	None	None	None	I
D/T	0.3479	ambiguous	0.4388	ambiguous	0.114	Stabilizing	0.157	N	0.399	neutral	None	None	None	None	I
D/V	0.3527	ambiguous	0.4356	ambiguous	0.214	Stabilizing	0.497	N	0.502	neutral	N	0.493941081	None	None	I
D/W	0.9531	likely_pathogenic	0.9677	pathogenic	0.155	Stabilizing	0.968	D	0.61	neutral	None	None	None	None	I
D/Y	0.4668	ambiguous	0.5306	ambiguous	0.279	Stabilizing	0.859	D	0.519	neutral	N	0.49444806	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.