TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3194	9805;9806;9807	chr2:178766504;178766503;178766502	chr2:179631231;179631230;179631229
N2AB	3194	9805;9806;9807	chr2:178766504;178766503;178766502	chr2:179631231;179631230;179631229
N2A	3194	9805;9806;9807	chr2:178766504;178766503;178766502	chr2:179631231;179631230;179631229
N2B	3148	9667;9668;9669	chr2:178766504;178766503;178766502	chr2:179631231;179631230;179631229
Novex-1	3148	9667;9668;9669	chr2:178766504;178766503;178766502	chr2:179631231;179631230;179631229
Novex-2	3148	9667;9668;9669	chr2:178766504;178766503;178766502	chr2:179631231;179631230;179631229
Novex-3	3194	9805;9806;9807	chr2:178766504;178766503;178766502	chr2:179631231;179631230;179631229

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-22
• Domain position: 48
• Structural Position: 121
• Q(SASA): 0.2127
• 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/D	rs1420659953	-2.253	0.523	N	0.645	0.329	0.253205268125	gnomAD-4.0.0	6.84082E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15934E-05	0
H/R	None	None	0.523	N	0.649	0.328	0.332133492242	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
H/Y	rs1420659953	None	0.001	N	0.175	0.103	0.139678290688	gnomAD-4.0.0	1.36816E-06	None	None	None	None	N	None	5.97407E-05	0	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	0.7165	likely_pathogenic	0.8643	pathogenic	-1.764	Destabilizing	0.228	N	0.605	neutral	None	None	None	None	N
H/C	0.3435	ambiguous	0.4028	ambiguous	-0.923	Destabilizing	0.983	D	0.655	neutral	None	None	None	None	N
H/D	0.6957	likely_pathogenic	0.8665	pathogenic	-1.631	Destabilizing	0.523	D	0.645	neutral	N	0.499667311	None	None	N
H/E	0.6683	likely_pathogenic	0.8409	pathogenic	-1.444	Destabilizing	0.593	D	0.583	neutral	None	None	None	None	N
H/F	0.3692	ambiguous	0.449	ambiguous	0.181	Stabilizing	0.001	N	0.339	neutral	None	None	None	None	N
H/G	0.7845	likely_pathogenic	0.9018	pathogenic	-2.193	Highly Destabilizing	0.593	D	0.626	neutral	None	None	None	None	N
H/I	0.486	ambiguous	0.6251	pathogenic	-0.495	Destabilizing	0.418	N	0.671	neutral	None	None	None	None	N
H/K	0.7463	likely_pathogenic	0.8819	pathogenic	-1.142	Destabilizing	0.418	N	0.633	neutral	None	None	None	None	N
H/L	0.2116	likely_benign	0.3201	benign	-0.495	Destabilizing	0.101	N	0.607	neutral	N	0.452576554	None	None	N
H/M	0.6051	likely_pathogenic	0.7158	pathogenic	-0.696	Destabilizing	0.94	D	0.63	neutral	None	None	None	None	N
H/N	0.2596	likely_benign	0.4316	ambiguous	-1.695	Destabilizing	0.523	D	0.606	neutral	N	0.499531806	None	None	N
H/P	0.7042	likely_pathogenic	0.88	pathogenic	-0.907	Destabilizing	0.921	D	0.656	neutral	N	0.499667311	None	None	N
H/Q	0.4827	ambiguous	0.682	pathogenic	-1.3	Destabilizing	0.794	D	0.65	neutral	N	0.499531806	None	None	N
H/R	0.4943	ambiguous	0.7193	pathogenic	-1.431	Destabilizing	0.523	D	0.649	neutral	N	0.498993076	None	None	N
H/S	0.586	likely_pathogenic	0.7676	pathogenic	-1.814	Destabilizing	0.418	N	0.605	neutral	None	None	None	None	N
H/T	0.5838	likely_pathogenic	0.783	pathogenic	-1.51	Destabilizing	0.593	D	0.643	neutral	None	None	None	None	N
H/V	0.4584	ambiguous	0.5838	pathogenic	-0.907	Destabilizing	0.418	N	0.661	neutral	None	None	None	None	N
H/W	0.4397	ambiguous	0.5275	ambiguous	0.735	Stabilizing	0.836	D	0.625	neutral	None	None	None	None	N
H/Y	0.1053	likely_benign	0.1573	benign	0.534	Stabilizing	0.001	N	0.175	neutral	N	0.360935011	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.