TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6958	21097;21098;21099	chr2:178724503;178724502;178724501	chr2:179589230;179589229;179589228
N2AB	6641	20146;20147;20148	chr2:178724503;178724502;178724501	chr2:179589230;179589229;179589228
N2A	5714	17365;17366;17367	chr2:178724503;178724502;178724501	chr2:179589230;179589229;179589228
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: ACG
• RefSeq wild type template codon: TGC
• Domain: Ig-54
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.7984
• 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	0.185	0.108	0.215869574891	gnomAD-4.0.0	1.60919E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.90225E-06	0	0
T/M	rs371824963	0.112	0.282	N	0.163	0.183	None	gnomAD-2.1.1	2.44E-05	None	None	None	None	I	None	0	0	None	0	1.11794E-04	None	3.32E-05	None	0	2.69E-05	0
T/M	rs371824963	0.112	0.282	N	0.163	0.183	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/M	rs371824963	0.112	0.282	N	0.163	0.183	None	gnomAD-4.0.0	1.05806E-05	None	None	None	None	I	None	0	0	None	0	4.47688E-05	None	0	1.65453E-04	1.02167E-05	1.10263E-05	1.60932E-05

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	0.072	likely_benign	0.0767	benign	-0.54	Destabilizing	0.139	N	0.185	neutral	N	0.478070266	None	None	I
T/C	0.4365	ambiguous	0.4818	ambiguous	-0.33	Destabilizing	0.981	D	0.316	neutral	None	None	None	None	I
T/D	0.296	likely_benign	0.3504	ambiguous	-0.002	Destabilizing	0.704	D	0.322	neutral	None	None	None	None	I
T/E	0.1971	likely_benign	0.2202	benign	-0.061	Destabilizing	0.329	N	0.297	neutral	None	None	None	None	I
T/F	0.1853	likely_benign	0.2065	benign	-0.909	Destabilizing	0.893	D	0.393	neutral	None	None	None	None	I
T/G	0.239	likely_benign	0.2518	benign	-0.71	Destabilizing	0.495	N	0.277	neutral	None	None	None	None	I
T/H	0.1685	likely_benign	0.1935	benign	-1.04	Destabilizing	0.944	D	0.305	neutral	None	None	None	None	I
T/I	0.1265	likely_benign	0.1365	benign	-0.201	Destabilizing	0.543	D	0.361	neutral	None	None	None	None	I
T/K	0.1078	likely_benign	0.1159	benign	-0.509	Destabilizing	0.002	N	0.112	neutral	N	0.483745445	None	None	I
T/L	0.0826	likely_benign	0.086	benign	-0.201	Destabilizing	0.069	N	0.242	neutral	None	None	None	None	I
T/M	0.0735	likely_benign	0.0741	benign	0.094	Stabilizing	0.282	N	0.163	neutral	N	0.512665629	None	None	I
T/N	0.0997	likely_benign	0.1098	benign	-0.312	Destabilizing	0.495	N	0.22	neutral	None	None	None	None	I
T/P	0.1298	likely_benign	0.1536	benign	-0.284	Destabilizing	0.784	D	0.357	neutral	N	0.48897492	None	None	I
T/Q	0.1426	likely_benign	0.1573	benign	-0.569	Destabilizing	0.704	D	0.356	neutral	None	None	None	None	I
T/R	0.0827	likely_benign	0.0886	benign	-0.214	Destabilizing	0.014	N	0.165	neutral	N	0.475166034	None	None	I
T/S	0.104	likely_benign	0.1117	benign	-0.553	Destabilizing	0.01	N	0.099	neutral	N	0.467911987	None	None	I
T/V	0.1109	likely_benign	0.1129	benign	-0.284	Destabilizing	0.329	N	0.239	neutral	None	None	None	None	I
T/W	0.4221	ambiguous	0.4587	ambiguous	-0.858	Destabilizing	0.995	D	0.291	neutral	None	None	None	None	I
T/Y	0.2086	likely_benign	0.2364	benign	-0.603	Destabilizing	0.944	D	0.368	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.