TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7184	21775;21776;21777	chr2:178723550;178723549;178723548	chr2:179588277;179588276;179588275
N2AB	6867	20824;20825;20826	chr2:178723550;178723549;178723548	chr2:179588277;179588276;179588275
N2A	5940	18043;18044;18045	chr2:178723550;178723549;178723548	chr2:179588277;179588276;179588275
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-56
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.3164
• 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
N/D	rs1366031789	-1.06	0.704	D	0.401	0.234	0.322786055943	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
N/D	rs1366031789	-1.06	0.704	D	0.401	0.234	0.322786055943	gnomAD-4.0.0	6.36876E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.73378E-05	0
N/S	None	None	0.31	N	0.136	0.107	0.171388866994	gnomAD-4.0.0	1.5922E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85969E-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
N/A	0.2638	likely_benign	0.2761	benign	-1.205	Destabilizing	0.759	D	0.39	neutral	None	None	None	None	N
N/C	0.3584	ambiguous	0.3928	ambiguous	-0.181	Destabilizing	0.999	D	0.507	neutral	None	None	None	None	N
N/D	0.1231	likely_benign	0.13	benign	-0.542	Destabilizing	0.704	D	0.401	neutral	D	0.525536139	None	None	N
N/E	0.391	ambiguous	0.4025	ambiguous	-0.377	Destabilizing	0.17	N	0.167	neutral	None	None	None	None	N
N/F	0.5589	ambiguous	0.5889	pathogenic	-0.696	Destabilizing	0.991	D	0.52	neutral	None	None	None	None	N
N/G	0.3245	likely_benign	0.3482	ambiguous	-1.592	Destabilizing	0.863	D	0.352	neutral	None	None	None	None	N
N/H	0.1073	likely_benign	0.1127	benign	-0.937	Destabilizing	0.996	D	0.413	neutral	N	0.49427187	None	None	N
N/I	0.2581	likely_benign	0.275	benign	-0.181	Destabilizing	0.134	N	0.393	neutral	D	0.530539314	None	None	N
N/K	0.3463	ambiguous	0.3609	ambiguous	-0.161	Destabilizing	0.92	D	0.339	neutral	N	0.483417371	None	None	N
N/L	0.2972	likely_benign	0.3117	benign	-0.181	Destabilizing	0.884	D	0.467	neutral	None	None	None	None	N
N/M	0.38	ambiguous	0.3929	ambiguous	0.166	Stabilizing	0.991	D	0.476	neutral	None	None	None	None	N
N/P	0.8375	likely_pathogenic	0.8579	pathogenic	-0.494	Destabilizing	0.991	D	0.439	neutral	None	None	None	None	N
N/Q	0.3492	ambiguous	0.3577	ambiguous	-0.706	Destabilizing	0.982	D	0.372	neutral	None	None	None	None	N
N/R	0.3144	likely_benign	0.3233	benign	-0.19	Destabilizing	0.939	D	0.366	neutral	None	None	None	None	N
N/S	0.0805	likely_benign	0.0861	benign	-1.041	Destabilizing	0.31	N	0.136	neutral	N	0.461831377	None	None	N
N/T	0.1497	likely_benign	0.1602	benign	-0.665	Destabilizing	0.852	D	0.352	neutral	N	0.475531393	None	None	N
N/V	0.2736	likely_benign	0.2877	benign	-0.494	Destabilizing	0.884	D	0.465	neutral	None	None	None	None	N
N/W	0.7384	likely_pathogenic	0.7574	pathogenic	-0.349	Destabilizing	0.999	D	0.586	neutral	None	None	None	None	N
N/Y	0.1831	likely_benign	0.1935	benign	-0.156	Destabilizing	0.996	D	0.493	neutral	N	0.508649338	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.