TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28755	86488;86489;86490	chr2:178559869;178559868;178559867	chr2:179424596;179424595;179424594
N2AB	27114	81565;81566;81567	chr2:178559869;178559868;178559867	chr2:179424596;179424595;179424594
N2A	26187	78784;78785;78786	chr2:178559869;178559868;178559867	chr2:179424596;179424595;179424594
N2B	19690	59293;59294;59295	chr2:178559869;178559868;178559867	chr2:179424596;179424595;179424594
Novex-1	19815	59668;59669;59670	chr2:178559869;178559868;178559867	chr2:179424596;179424595;179424594
Novex-2	19882	59869;59870;59871	chr2:178559869;178559868;178559867	chr2:179424596;179424595;179424594
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-144
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.5619
• 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
D/A	rs1702996133	None	0.379	N	0.41	0.225	0.371531589858	gnomAD-4.0.0	1.36965E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79899E-06	0	0
D/V	None	None	0.379	N	0.448	0.29	0.496165130923	gnomAD-4.0.0	4.10895E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.39696E-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
D/A	0.1976	likely_benign	0.2336	benign	0.003	Stabilizing	0.379	N	0.41	neutral	N	0.520740821	None	None	I
D/C	0.5495	ambiguous	0.6257	pathogenic	-0.126	Destabilizing	0.992	D	0.576	neutral	None	None	None	None	I
D/E	0.1523	likely_benign	0.164	benign	-0.295	Destabilizing	0.002	N	0.203	neutral	N	0.400548058	None	None	I
D/F	0.5102	ambiguous	0.5658	pathogenic	-0.034	Destabilizing	0.85	D	0.548	neutral	None	None	None	None	I
D/G	0.2994	likely_benign	0.3324	benign	-0.138	Destabilizing	0.549	D	0.397	neutral	N	0.502848493	None	None	I
D/H	0.2755	likely_benign	0.3199	benign	0.471	Stabilizing	0.896	D	0.466	neutral	N	0.521780971	None	None	I
D/I	0.2611	likely_benign	0.3051	benign	0.311	Stabilizing	0.739	D	0.493	neutral	None	None	None	None	I
D/K	0.4881	ambiguous	0.555	ambiguous	0.381	Stabilizing	0.447	N	0.393	neutral	None	None	None	None	I
D/L	0.3077	likely_benign	0.3659	ambiguous	0.311	Stabilizing	0.005	N	0.339	neutral	None	None	None	None	I
D/M	0.5192	ambiguous	0.5983	pathogenic	0.111	Stabilizing	0.955	D	0.553	neutral	None	None	None	None	I
D/N	0.1176	likely_benign	0.1335	benign	0.142	Stabilizing	0.549	D	0.423	neutral	N	0.521087538	None	None	I
D/P	0.869	likely_pathogenic	0.8624	pathogenic	0.229	Stabilizing	0.92	D	0.451	neutral	None	None	None	None	I
D/Q	0.3435	ambiguous	0.384	ambiguous	0.153	Stabilizing	0.739	D	0.391	neutral	None	None	None	None	I
D/R	0.4976	ambiguous	0.5472	ambiguous	0.629	Stabilizing	0.85	D	0.494	neutral	None	None	None	None	I
D/S	0.1499	likely_benign	0.1689	benign	0.045	Stabilizing	0.447	N	0.383	neutral	None	None	None	None	I
D/T	0.2541	likely_benign	0.2994	benign	0.156	Stabilizing	0.617	D	0.403	neutral	None	None	None	None	I
D/V	0.1646	likely_benign	0.1917	benign	0.229	Stabilizing	0.379	N	0.448	neutral	N	0.521434254	None	None	I
D/W	0.8608	likely_pathogenic	0.8818	pathogenic	0.022	Stabilizing	0.992	D	0.643	neutral	None	None	None	None	I
D/Y	0.2155	likely_benign	0.2439	benign	0.194	Stabilizing	0.963	D	0.549	neutral	N	0.521954329	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.