TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7499	22720;22721;22722	chr2:178722292;178722291;178722290	chr2:179587019;179587018;179587017
N2AB	7182	21769;21770;21771	chr2:178722292;178722291;178722290	chr2:179587019;179587018;179587017
N2A	6255	18988;18989;18990	chr2:178722292;178722291;178722290	chr2:179587019;179587018;179587017
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-59
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.4526
• 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
T/A	rs2078525840	None	0.186	N	0.32	0.117	0.163833314356	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/A	rs2078525840	None	0.186	N	0.32	0.117	0.163833314356	gnomAD-4.0.0	5.16597E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.64343E-06	0	0
T/I	None	None	0.982	N	0.438	0.248	0.467923293426	gnomAD-4.0.0	3.21709E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.77027E-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
T/A	0.0918	likely_benign	0.0924	benign	-0.371	Destabilizing	0.186	N	0.32	neutral	N	0.494154439	None	None	I
T/C	0.5559	ambiguous	0.5452	ambiguous	-0.164	Destabilizing	0.999	D	0.481	neutral	None	None	None	None	I
T/D	0.375	ambiguous	0.3727	ambiguous	0.106	Stabilizing	0.819	D	0.391	neutral	None	None	None	None	I
T/E	0.263	likely_benign	0.2563	benign	0.008	Stabilizing	0.883	D	0.391	neutral	None	None	None	None	I
T/F	0.1838	likely_benign	0.1919	benign	-1.004	Destabilizing	0.29	N	0.376	neutral	None	None	None	None	I
T/G	0.2936	likely_benign	0.3154	benign	-0.446	Destabilizing	0.974	D	0.493	neutral	None	None	None	None	I
T/H	0.2389	likely_benign	0.2346	benign	-0.813	Destabilizing	0.993	D	0.538	neutral	None	None	None	None	I
T/I	0.1663	likely_benign	0.1666	benign	-0.294	Destabilizing	0.982	D	0.438	neutral	N	0.484340111	None	None	I
T/K	0.1783	likely_benign	0.1736	benign	-0.229	Destabilizing	0.888	D	0.407	neutral	N	0.499288113	None	None	I
T/L	0.1097	likely_benign	0.1166	benign	-0.294	Destabilizing	0.813	D	0.391	neutral	None	None	None	None	I
T/M	0.0844	likely_benign	0.0857	benign	0.007	Stabilizing	0.998	D	0.477	neutral	None	None	None	None	I
T/N	0.1182	likely_benign	0.1194	benign	0.046	Stabilizing	0.819	D	0.4	neutral	None	None	None	None	I
T/P	0.2845	likely_benign	0.3182	benign	-0.295	Destabilizing	0.96	D	0.459	neutral	N	0.488036641	None	None	I
T/Q	0.2033	likely_benign	0.202	benign	-0.243	Destabilizing	0.471	N	0.255	neutral	None	None	None	None	I
T/R	0.1473	likely_benign	0.1474	benign	0.019	Stabilizing	0.993	D	0.442	neutral	N	0.519820888	None	None	I
T/S	0.0994	likely_benign	0.1042	benign	-0.146	Destabilizing	0.018	N	0.12	neutral	N	0.416077658	None	None	I
T/V	0.1358	likely_benign	0.1367	benign	-0.295	Destabilizing	0.938	D	0.329	neutral	None	None	None	None	I
T/W	0.5496	ambiguous	0.5567	ambiguous	-1.008	Destabilizing	1.0	D	0.543	neutral	None	None	None	None	I
T/Y	0.2634	likely_benign	0.2548	benign	-0.714	Destabilizing	0.99	D	0.531	neutral	None	None	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.