TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7332	22219;22220;22221	chr2:178722905;178722904;178722903	chr2:179587632;179587631;179587630
N2AB	7015	21268;21269;21270	chr2:178722905;178722904;178722903	chr2:179587632;179587631;179587630
N2A	6088	18487;18488;18489	chr2:178722905;178722904;178722903	chr2:179587632;179587631;179587630
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-58
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.524
• 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
L/Q	rs369522109	-0.529	0.966	N	0.351	0.509	None	gnomAD-2.1.1	2.43E-05	None	None	None	None	I	None	3.89257E-04	0	None	0	0	None	0	None	0	0	0
L/Q	rs369522109	-0.529	0.966	N	0.351	0.509	None	gnomAD-3.1.2	8.54E-05	None	None	None	None	I	None	2.89436E-04	6.55E-05	0	0	0	None	0	0	0	0	0
L/Q	rs369522109	-0.529	0.966	N	0.351	0.509	None	gnomAD-4.0.0	1.36422E-05	None	None	None	None	I	None	2.80404E-04	1.67017E-05	None	0	0	None	0	0	0	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
L/A	0.1114	likely_benign	0.1589	benign	-1.899	Destabilizing	0.067	N	0.207	neutral	None	None	None	None	I
L/C	0.3449	ambiguous	0.4726	ambiguous	-1.161	Destabilizing	0.998	D	0.263	neutral	None	None	None	None	I
L/D	0.475	ambiguous	0.6819	pathogenic	-1.451	Destabilizing	0.949	D	0.411	neutral	None	None	None	None	I
L/E	0.1708	likely_benign	0.246	benign	-1.339	Destabilizing	0.949	D	0.429	neutral	None	None	None	None	I
L/F	0.0908	likely_benign	0.1211	benign	-1.102	Destabilizing	0.949	D	0.253	neutral	None	None	None	None	I
L/G	0.3306	likely_benign	0.5114	ambiguous	-2.328	Highly Destabilizing	0.842	D	0.412	neutral	None	None	None	None	I
L/H	0.1185	likely_benign	0.1824	benign	-1.503	Destabilizing	0.998	D	0.346	neutral	None	None	None	None	I
L/I	0.0672	likely_benign	0.0739	benign	-0.732	Destabilizing	0.007	N	0.11	neutral	None	None	None	None	I
L/K	0.1173	likely_benign	0.1606	benign	-1.372	Destabilizing	0.842	D	0.397	neutral	None	None	None	None	I
L/M	0.0828	likely_benign	0.0887	benign	-0.636	Destabilizing	0.267	N	0.224	neutral	N	0.45152117	None	None	I
L/N	0.2711	likely_benign	0.4091	ambiguous	-1.391	Destabilizing	0.949	D	0.397	neutral	None	None	None	None	I
L/P	0.497	ambiguous	0.7791	pathogenic	-1.093	Destabilizing	0.966	D	0.397	neutral	N	0.518015521	None	None	I
L/Q	0.0734	likely_benign	0.0974	benign	-1.404	Destabilizing	0.966	D	0.351	neutral	N	0.450251734	None	None	I
L/R	0.0814	likely_benign	0.1233	benign	-0.942	Destabilizing	0.966	D	0.362	neutral	N	0.445480632	None	None	I
L/S	0.1293	likely_benign	0.2068	benign	-2.07	Highly Destabilizing	0.172	N	0.196	neutral	None	None	None	None	I
L/T	0.0992	likely_benign	0.132	benign	-1.82	Destabilizing	0.728	D	0.269	neutral	None	None	None	None	I
L/V	0.0625	likely_benign	0.066	benign	-1.093	Destabilizing	0.022	N	0.097	neutral	N	0.393795444	None	None	I
L/W	0.1459	likely_benign	0.2317	benign	-1.283	Destabilizing	0.998	D	0.368	neutral	None	None	None	None	I
L/Y	0.2285	likely_benign	0.3369	benign	-1.02	Destabilizing	0.991	D	0.286	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.