TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7932	24019;24020;24021	chr2:178719698;178719697;178719696	chr2:179584425;179584424;179584423
N2AB	7615	23068;23069;23070	chr2:178719698;178719697;178719696	chr2:179584425;179584424;179584423
N2A	6688	20287;20288;20289	chr2:178719698;178719697;178719696	chr2:179584425;179584424;179584423
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: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-64
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.773
• 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/E	rs1271514661	None	0.117	N	0.262	0.05	0.107399877778	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/E	rs1271514661	None	0.117	N	0.262	0.05	0.107399877778	gnomAD-4.0.0	6.57428E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47024E-05	0	0
D/G	None	None	None	N	0.19	0.116	0.0666544352282	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	0.1381	likely_benign	0.2214	benign	-0.399	Destabilizing	0.027	N	0.289	neutral	N	0.454415121	None	None	N
D/C	0.4659	ambiguous	0.6282	pathogenic	-0.033	Destabilizing	0.935	D	0.265	neutral	None	None	None	None	N
D/E	0.2005	likely_benign	0.2974	benign	-0.355	Destabilizing	0.117	N	0.262	neutral	N	0.452337979	None	None	N
D/F	0.5108	ambiguous	0.6626	pathogenic	-0.327	Destabilizing	0.555	D	0.286	neutral	None	None	None	None	N
D/G	0.0867	likely_benign	0.1314	benign	-0.635	Destabilizing	None	N	0.19	neutral	N	0.417380727	None	None	N
D/H	0.2185	likely_benign	0.3245	benign	-0.382	Destabilizing	0.915	D	0.237	neutral	N	0.474431933	None	None	N
D/I	0.3762	ambiguous	0.55	ambiguous	0.187	Stabilizing	0.005	N	0.271	neutral	None	None	None	None	N
D/K	0.3347	likely_benign	0.4945	ambiguous	-0.118	Destabilizing	0.149	N	0.337	neutral	None	None	None	None	N
D/L	0.3443	ambiguous	0.506	ambiguous	0.187	Stabilizing	0.081	N	0.357	neutral	None	None	None	None	N
D/M	0.582	likely_pathogenic	0.7327	pathogenic	0.457	Stabilizing	0.824	D	0.255	neutral	None	None	None	None	N
D/N	0.0803	likely_benign	0.0963	benign	-0.294	Destabilizing	0.117	N	0.269	neutral	N	0.479085334	None	None	N
D/P	0.6587	likely_pathogenic	0.7776	pathogenic	0.015	Stabilizing	0.555	D	0.281	neutral	None	None	None	None	N
D/Q	0.3103	likely_benign	0.4825	ambiguous	-0.229	Destabilizing	0.555	D	0.259	neutral	None	None	None	None	N
D/R	0.3371	likely_benign	0.5102	ambiguous	0.061	Stabilizing	0.38	N	0.29	neutral	None	None	None	None	N
D/S	0.0816	likely_benign	0.113	benign	-0.465	Destabilizing	0.001	N	0.132	neutral	None	None	None	None	N
D/T	0.1693	likely_benign	0.2527	benign	-0.29	Destabilizing	0.081	N	0.313	neutral	None	None	None	None	N
D/V	0.2247	likely_benign	0.3394	benign	0.015	Stabilizing	0.062	N	0.355	neutral	N	0.47724309	None	None	N
D/W	0.818	likely_pathogenic	0.9058	pathogenic	-0.223	Destabilizing	0.935	D	0.422	neutral	None	None	None	None	N
D/Y	0.2236	likely_benign	0.3219	benign	-0.125	Destabilizing	0.741	D	0.265	neutral	N	0.473128487	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.