TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25861	77806;77807;77808	chr2:178568551;178568550;178568549	chr2:179433278;179433277;179433276
N2AB	24220	72883;72884;72885	chr2:178568551;178568550;178568549	chr2:179433278;179433277;179433276
N2A	23293	70102;70103;70104	chr2:178568551;178568550;178568549	chr2:179433278;179433277;179433276
N2B	16796	50611;50612;50613	chr2:178568551;178568550;178568549	chr2:179433278;179433277;179433276
Novex-1	16921	50986;50987;50988	chr2:178568551;178568550;178568549	chr2:179433278;179433277;179433276
Novex-2	16988	51187;51188;51189	chr2:178568551;178568550;178568549	chr2:179433278;179433277;179433276
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-136
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.3526
• 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
H/L	rs769029689	None	0.012	N	0.276	0.251	0.40146981186	gnomAD-4.0.0	8.21246E-06	None	None	None	None	N	None	0	2.23644E-05	None	0	0	None	0	0	8.99672E-06	0	1.65744E-05
H/P	rs769029689	0.116	0.21	N	0.382	0.272	0.337135696972	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
H/P	rs769029689	0.116	0.21	N	0.382	0.272	0.337135696972	gnomAD-4.0.0	6.84377E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99679E-07	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	0.1631	likely_benign	0.128	benign	0.411	Stabilizing	0.001	N	0.121	neutral	None	None	None	None	N
H/C	0.0943	likely_benign	0.0868	benign	1.036	Stabilizing	0.901	D	0.434	neutral	None	None	None	None	N
H/D	0.1806	likely_benign	0.1651	benign	0.226	Stabilizing	0.028	N	0.329	neutral	N	0.448766079	None	None	N
H/E	0.2449	likely_benign	0.2211	benign	0.241	Stabilizing	0.036	N	0.211	neutral	None	None	None	None	N
H/F	0.2355	likely_benign	0.2116	benign	0.844	Stabilizing	0.46	N	0.426	neutral	None	None	None	None	N
H/G	0.179	likely_benign	0.1503	benign	0.129	Stabilizing	0.016	N	0.263	neutral	None	None	None	None	N
H/I	0.2096	likely_benign	0.1827	benign	1.127	Stabilizing	0.002	N	0.197	neutral	None	None	None	None	N
H/K	0.1574	likely_benign	0.1586	benign	0.471	Stabilizing	None	N	0.15	neutral	None	None	None	None	N
H/L	0.0922	likely_benign	0.0832	benign	1.127	Stabilizing	0.012	N	0.276	neutral	N	0.461023301	None	None	N
H/M	0.2841	likely_benign	0.2463	benign	0.999	Stabilizing	0.749	D	0.467	neutral	None	None	None	None	N
H/N	0.0646	likely_benign	0.0569	benign	0.659	Stabilizing	None	N	0.137	neutral	N	0.438530443	None	None	N
H/P	0.4758	ambiguous	0.4533	ambiguous	0.915	Stabilizing	0.21	N	0.382	neutral	N	0.481742764	None	None	N
H/Q	0.1059	likely_benign	0.0967	benign	0.725	Stabilizing	0.002	N	0.183	neutral	N	0.419077891	None	None	N
H/R	0.0882	likely_benign	0.0868	benign	-0.102	Destabilizing	0.061	N	0.209	neutral	N	0.424331782	None	None	N
H/S	0.1095	likely_benign	0.0881	benign	0.728	Stabilizing	0.001	N	0.133	neutral	None	None	None	None	N
H/T	0.1282	likely_benign	0.1041	benign	0.836	Stabilizing	0.001	N	0.115	neutral	None	None	None	None	N
H/V	0.148	likely_benign	0.1299	benign	0.915	Stabilizing	0.036	N	0.281	neutral	None	None	None	None	N
H/W	0.3865	ambiguous	0.3809	ambiguous	0.776	Stabilizing	0.901	D	0.393	neutral	None	None	None	None	N
H/Y	0.1009	likely_benign	0.0948	benign	1.16	Stabilizing	0.391	N	0.235	neutral	N	0.49836818	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.