TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9251	27976;27977;27978	chr2:178712079;178712078;178712077	chr2:179576806;179576805;179576804
N2AB	8934	27025;27026;27027	chr2:178712079;178712078;178712077	chr2:179576806;179576805;179576804
N2A	8007	24244;24245;24246	chr2:178712079;178712078;178712077	chr2:179576806;179576805;179576804
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-78
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1894
• 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
Y/C	rs2076738638	None	None	N	0.201	0.174	0.382592752248	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	4.78927E-04
Y/C	rs2076738638	None	None	N	0.201	0.174	0.382592752248	gnomAD-4.0.0	3.0447E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.2049E-06	0	6.80596E-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
Y/A	0.2153	likely_benign	0.2925	benign	-2.661	Highly Destabilizing	0.002	N	0.321	neutral	None	None	None	None	N
Y/C	0.055	likely_benign	0.0774	benign	-1.645	Destabilizing	None	N	0.201	neutral	N	0.521074469	None	None	N
Y/D	0.3735	ambiguous	0.5571	ambiguous	-2.298	Highly Destabilizing	0.014	N	0.447	neutral	D	0.535158487	None	None	N
Y/E	0.5671	likely_pathogenic	0.7194	pathogenic	-2.114	Highly Destabilizing	0.009	N	0.353	neutral	None	None	None	None	N
Y/F	0.0856	likely_benign	0.1173	benign	-0.908	Destabilizing	None	N	0.195	neutral	N	0.50471815	None	None	N
Y/G	0.2334	likely_benign	0.2943	benign	-3.079	Highly Destabilizing	0.009	N	0.355	neutral	None	None	None	None	N
Y/H	0.1484	likely_benign	0.2382	benign	-1.609	Destabilizing	0.196	N	0.489	neutral	N	0.495426663	None	None	N
Y/I	0.2606	likely_benign	0.3828	ambiguous	-1.315	Destabilizing	0.009	N	0.315	neutral	None	None	None	None	N
Y/K	0.54	ambiguous	0.6714	pathogenic	-1.804	Destabilizing	0.009	N	0.369	neutral	None	None	None	None	N
Y/L	0.3169	likely_benign	0.385	ambiguous	-1.315	Destabilizing	0.001	N	0.297	neutral	None	None	None	None	N
Y/M	0.3964	ambiguous	0.4833	ambiguous	-1.133	Destabilizing	0.002	N	0.252	neutral	None	None	None	None	N
Y/N	0.1525	likely_benign	0.201	benign	-2.452	Highly Destabilizing	0.017	N	0.484	neutral	N	0.494281293	None	None	N
Y/P	0.8359	likely_pathogenic	0.895	pathogenic	-1.772	Destabilizing	0.085	N	0.553	neutral	None	None	None	None	N
Y/Q	0.3356	likely_benign	0.4688	ambiguous	-2.214	Highly Destabilizing	0.001	N	0.208	neutral	None	None	None	None	N
Y/R	0.3428	ambiguous	0.4679	ambiguous	-1.576	Destabilizing	0.022	N	0.5	neutral	None	None	None	None	N
Y/S	0.095	likely_benign	0.1279	benign	-2.949	Highly Destabilizing	None	N	0.234	neutral	D	0.522343905	None	None	N
Y/T	0.1882	likely_benign	0.2667	benign	-2.642	Highly Destabilizing	None	N	0.223	neutral	None	None	None	None	N
Y/V	0.1756	likely_benign	0.2473	benign	-1.772	Destabilizing	None	N	0.15	neutral	None	None	None	None	N
Y/W	0.3102	likely_benign	0.4563	ambiguous	-0.297	Destabilizing	0.245	N	0.495	neutral	None	None	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.