TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28103	84532;84533;84534	chr2:178561825;178561824;178561823	chr2:179426552;179426551;179426550
N2AB	26462	79609;79610;79611	chr2:178561825;178561824;178561823	chr2:179426552;179426551;179426550
N2A	25535	76828;76829;76830	chr2:178561825;178561824;178561823	chr2:179426552;179426551;179426550
N2B	19038	57337;57338;57339	chr2:178561825;178561824;178561823	chr2:179426552;179426551;179426550
Novex-1	19163	57712;57713;57714	chr2:178561825;178561824;178561823	chr2:179426552;179426551;179426550
Novex-2	19230	57913;57914;57915	chr2:178561825;178561824;178561823	chr2:179426552;179426551;179426550
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-92
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.5971
• 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
H/Q	rs749278779	0.145	None	N	0.049	0.13	0.0401082797425	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
H/Q	rs749278779	0.145	None	N	0.049	0.13	0.0401082797425	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
H/Q	rs749278779	0.145	None	N	0.049	0.13	0.0401082797425	gnomAD-4.0.0	3.84412E-06	None	None	None	None	I	None	0	5.08613E-05	None	0	0	None	0	0	0	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
H/A	0.1689	likely_benign	0.1442	benign	-0.22	Destabilizing	0.002	N	0.244	neutral	None	None	None	None	I
H/C	0.1295	likely_benign	0.1257	benign	0.488	Stabilizing	0.497	N	0.345	neutral	None	None	None	None	I
H/D	0.1326	likely_benign	0.1223	benign	-0.298	Destabilizing	None	N	0.107	neutral	N	0.417797306	None	None	I
H/E	0.1495	likely_benign	0.1322	benign	-0.221	Destabilizing	None	N	0.049	neutral	None	None	None	None	I
H/F	0.2954	likely_benign	0.2696	benign	0.925	Stabilizing	0.044	N	0.387	neutral	None	None	None	None	I
H/G	0.2364	likely_benign	0.2034	benign	-0.565	Destabilizing	0.004	N	0.291	neutral	None	None	None	None	I
H/I	0.1768	likely_benign	0.1652	benign	0.709	Stabilizing	0.009	N	0.38	neutral	None	None	None	None	I
H/K	0.1726	likely_benign	0.1455	benign	-0.118	Destabilizing	0.004	N	0.205	neutral	None	None	None	None	I
H/L	0.0937	likely_benign	0.0918	benign	0.709	Stabilizing	None	N	0.218	neutral	N	0.373371739	None	None	I
H/M	0.2734	likely_benign	0.2425	benign	0.46	Stabilizing	0.138	N	0.383	neutral	None	None	None	None	I
H/N	0.063	likely_benign	0.0643	benign	-0.241	Destabilizing	0.007	N	0.186	neutral	N	0.426203359	None	None	I
H/P	0.5046	ambiguous	0.4728	ambiguous	0.422	Stabilizing	0.028	N	0.356	neutral	N	0.476325535	None	None	I
H/Q	0.0892	likely_benign	0.0858	benign	-0.045	Destabilizing	None	N	0.049	neutral	N	0.326367226	None	None	I
H/R	0.1061	likely_benign	0.0967	benign	-0.733	Destabilizing	0.007	N	0.203	neutral	N	0.415391719	None	None	I
H/S	0.1321	likely_benign	0.1143	benign	-0.154	Destabilizing	None	N	0.111	neutral	None	None	None	None	I
H/T	0.1262	likely_benign	0.1103	benign	0.028	Stabilizing	0.004	N	0.288	neutral	None	None	None	None	I
H/V	0.132	likely_benign	0.1241	benign	0.422	Stabilizing	0.009	N	0.302	neutral	None	None	None	None	I
H/W	0.4471	ambiguous	0.3985	ambiguous	1.127	Stabilizing	0.788	D	0.316	neutral	None	None	None	None	I
H/Y	0.1026	likely_benign	0.0987	benign	1.23	Stabilizing	0.065	N	0.264	neutral	N	0.433305477	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.