TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18746	56461;56462;56463	chr2:178599665;178599664;178599663	chr2:179464392;179464391;179464390
N2AB	17105	51538;51539;51540	chr2:178599665;178599664;178599663	chr2:179464392;179464391;179464390
N2A	16178	48757;48758;48759	chr2:178599665;178599664;178599663	chr2:179464392;179464391;179464390
N2B	9681	29266;29267;29268	chr2:178599665;178599664;178599663	chr2:179464392;179464391;179464390
Novex-1	9806	29641;29642;29643	chr2:178599665;178599664;178599663	chr2:179464392;179464391;179464390
Novex-2	9873	29842;29843;29844	chr2:178599665;178599664;178599663	chr2:179464392;179464391;179464390
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-116
• Domain position: 59
• Structural Position: 135
• Q(SASA): 0.2097
• 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	None	None	0.139	N	0.281	0.161	0.21279746466	gnomAD-4.0.0	3.18579E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72243E-06	0	0
T/I	rs762145585	0.178	0.784	N	0.496	0.228	0.315609569513	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	5.59E-05	None	0	None	0	8.91E-06	0
T/I	rs762145585	0.178	0.784	N	0.496	0.228	0.315609569513	gnomAD-4.0.0	1.59294E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86134E-06	0	0
T/P	None	None	0.784	N	0.491	0.357	0.331365685468	gnomAD-4.0.0	1.59289E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86121E-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	0.0865	likely_benign	0.0804	benign	-0.801	Destabilizing	0.139	N	0.281	neutral	N	0.47185637	None	None	I
T/C	0.316	likely_benign	0.2917	benign	-0.622	Destabilizing	0.995	D	0.478	neutral	None	None	None	None	I
T/D	0.3371	likely_benign	0.3027	benign	-0.931	Destabilizing	0.704	D	0.453	neutral	None	None	None	None	I
T/E	0.2606	likely_benign	0.236	benign	-0.876	Destabilizing	0.495	N	0.452	neutral	None	None	None	None	I
T/F	0.2159	likely_benign	0.1841	benign	-0.694	Destabilizing	0.981	D	0.546	neutral	None	None	None	None	I
T/G	0.2539	likely_benign	0.2284	benign	-1.12	Destabilizing	0.329	N	0.526	neutral	None	None	None	None	I
T/H	0.2206	likely_benign	0.1816	benign	-1.481	Destabilizing	0.981	D	0.548	neutral	None	None	None	None	I
T/I	0.1252	likely_benign	0.1234	benign	-0.023	Destabilizing	0.784	D	0.496	neutral	N	0.453558611	None	None	I
T/K	0.1777	likely_benign	0.1595	benign	-0.892	Destabilizing	0.004	N	0.187	neutral	None	None	None	None	I
T/L	0.1065	likely_benign	0.1	benign	-0.023	Destabilizing	0.495	N	0.453	neutral	None	None	None	None	I
T/M	0.0939	likely_benign	0.0922	benign	0.227	Stabilizing	0.981	D	0.497	neutral	None	None	None	None	I
T/N	0.1152	likely_benign	0.1017	benign	-1.062	Destabilizing	0.425	N	0.284	neutral	N	0.425622648	None	None	I
T/P	0.6701	likely_pathogenic	0.6001	pathogenic	-0.248	Destabilizing	0.784	D	0.491	neutral	N	0.493098434	None	None	I
T/Q	0.2053	likely_benign	0.1871	benign	-1.139	Destabilizing	0.704	D	0.449	neutral	None	None	None	None	I
T/R	0.1704	likely_benign	0.1446	benign	-0.775	Destabilizing	0.007	N	0.217	neutral	None	None	None	None	I
T/S	0.0974	likely_benign	0.0892	benign	-1.241	Destabilizing	0.01	N	0.13	neutral	N	0.394126305	None	None	I
T/V	0.1171	likely_benign	0.1162	benign	-0.248	Destabilizing	0.704	D	0.284	neutral	None	None	None	None	I
T/W	0.6061	likely_pathogenic	0.5487	ambiguous	-0.723	Destabilizing	0.995	D	0.551	neutral	None	None	None	None	I
T/Y	0.2271	likely_benign	0.193	benign	-0.447	Destabilizing	0.981	D	0.545	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.