TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6419	19480;19481;19482	chr2:178728671;178728670;178728669	chr2:179593398;179593397;179593396
N2AB	6102	18529;18530;18531	chr2:178728671;178728670;178728669	chr2:179593398;179593397;179593396
N2A	5175	15748;15749;15750	chr2:178728671;178728670;178728669	chr2:179593398;179593397;179593396
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: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-48
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1742
• Predicted PPI site: N

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/F	None	None	0.002	N	0.222	0.1	0.277317399466	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
L/R	None	None	0.004	N	0.515	0.229	0.645662332294	gnomAD-4.0.0	3.1847E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71981E-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
L/A	0.407	ambiguous	0.3651	ambiguous	-2.411	Highly Destabilizing	0.129	N	0.481	neutral	None	None	None	None	N
L/C	0.4746	ambiguous	0.4264	ambiguous	-1.721	Destabilizing	0.983	D	0.541	neutral	None	None	None	None	N
L/D	0.7604	likely_pathogenic	0.7023	pathogenic	-2.393	Highly Destabilizing	0.716	D	0.605	neutral	None	None	None	None	N
L/E	0.3237	likely_benign	0.2997	benign	-2.257	Highly Destabilizing	0.418	N	0.585	neutral	None	None	None	None	N
L/F	0.0704	likely_benign	0.0607	benign	-1.517	Destabilizing	0.002	N	0.222	neutral	N	0.395023942	None	None	N
L/G	0.6585	likely_pathogenic	0.6166	pathogenic	-2.873	Highly Destabilizing	0.418	N	0.564	neutral	None	None	None	None	N
L/H	0.1965	likely_benign	0.1593	benign	-2.171	Highly Destabilizing	0.655	D	0.593	neutral	N	0.454441574	None	None	N
L/I	0.1358	likely_benign	0.1161	benign	-1.121	Destabilizing	0.213	N	0.437	neutral	N	0.455642889	None	None	N
L/K	0.3505	ambiguous	0.304	benign	-1.787	Destabilizing	0.264	N	0.524	neutral	None	None	None	None	N
L/M	0.0938	likely_benign	0.0897	benign	-1.024	Destabilizing	0.061	N	0.371	neutral	None	None	None	None	N
L/N	0.4278	ambiguous	0.3805	ambiguous	-1.883	Destabilizing	0.716	D	0.612	neutral	None	None	None	None	N
L/P	0.9854	likely_pathogenic	0.9762	pathogenic	-1.528	Destabilizing	0.794	D	0.597	neutral	N	0.498145276	None	None	N
L/Q	0.1319	likely_benign	0.1211	benign	-1.903	Destabilizing	0.716	D	0.575	neutral	None	None	None	None	N
L/R	0.2552	likely_benign	0.2241	benign	-1.319	Destabilizing	0.004	N	0.515	neutral	N	0.507061369	None	None	N
L/S	0.3	likely_benign	0.2527	benign	-2.585	Highly Destabilizing	0.027	N	0.533	neutral	None	None	None	None	N
L/T	0.2621	likely_benign	0.2323	benign	-2.321	Highly Destabilizing	0.01	N	0.449	neutral	None	None	None	None	N
L/V	0.1269	likely_benign	0.1117	benign	-1.528	Destabilizing	0.101	N	0.44	neutral	N	0.514699417	None	None	N
L/W	0.1392	likely_benign	0.1149	benign	-1.78	Destabilizing	0.951	D	0.556	neutral	None	None	None	None	N
L/Y	0.1836	likely_benign	0.1569	benign	-1.535	Destabilizing	0.002	N	0.442	neutral	None	None	None	None	N

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.