TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5093	15502;15503;15504	chr2:178734547;178734546;178734545	chr2:179599274;179599273;179599272
N2AB	4776	14551;14552;14553	chr2:178734547;178734546;178734545	chr2:179599274;179599273;179599272
N2A	3849	11770;11771;11772	chr2:178734547;178734546;178734545	chr2:179599274;179599273;179599272
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: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-34
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.4497
• 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/I	None	None	0.001	N	0.242	0.1	0.26169431596	gnomAD-4.0.0	6.87004E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02341E-07	0	0
L/V	rs764663290	-0.815	None	N	0.281	0.108	0.263140351381	gnomAD-2.1.1	2.47E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.71233E-04	None	0	9.06E-06	0
L/V	rs764663290	-0.815	None	N	0.281	0.108	0.263140351381	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/V	rs764663290	-0.815	None	N	0.281	0.108	0.263140351381	gnomAD-4.0.0	1.43052E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.6514E-06	1.55466E-04	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	0.1886	likely_benign	0.136	benign	-1.339	Destabilizing	0.055	N	0.383	neutral	None	None	None	None	N
L/C	0.3725	ambiguous	0.3059	benign	-0.815	Destabilizing	0.667	D	0.471	neutral	None	None	None	None	N
L/D	0.5368	ambiguous	0.4268	ambiguous	-0.846	Destabilizing	0.22	N	0.477	neutral	None	None	None	None	N
L/E	0.242	likely_benign	0.2068	benign	-0.876	Destabilizing	0.124	N	0.454	neutral	None	None	None	None	N
L/F	0.0911	likely_benign	0.0776	benign	-0.961	Destabilizing	0.001	N	0.297	neutral	None	None	None	None	N
L/G	0.4831	ambiguous	0.3643	ambiguous	-1.616	Destabilizing	0.22	N	0.465	neutral	None	None	None	None	N
L/H	0.1405	likely_benign	0.117	benign	-0.766	Destabilizing	0.001	N	0.47	neutral	None	None	None	None	N
L/I	0.0657	likely_benign	0.0613	benign	-0.675	Destabilizing	0.001	N	0.242	neutral	N	0.416806214	None	None	N
L/K	0.1774	likely_benign	0.1482	benign	-0.973	Destabilizing	0.124	N	0.476	neutral	None	None	None	None	N
L/M	0.0851	likely_benign	0.081	benign	-0.544	Destabilizing	0.497	N	0.441	neutral	None	None	None	None	N
L/N	0.2632	likely_benign	0.202	benign	-0.759	Destabilizing	0.22	N	0.481	neutral	None	None	None	None	N
L/P	0.6735	likely_pathogenic	0.5307	ambiguous	-0.864	Destabilizing	0.602	D	0.544	neutral	N	0.514457906	None	None	N
L/Q	0.1089	likely_benign	0.09	benign	-0.961	Destabilizing	0.008	N	0.423	neutral	N	0.433241942	None	None	N
L/R	0.1336	likely_benign	0.107	benign	-0.326	Destabilizing	0.175	N	0.512	neutral	N	0.449565866	None	None	N
L/S	0.1699	likely_benign	0.1309	benign	-1.299	Destabilizing	0.055	N	0.435	neutral	None	None	None	None	N
L/T	0.1273	likely_benign	0.1021	benign	-1.215	Destabilizing	0.004	N	0.294	neutral	None	None	None	None	N
L/V	0.0632	likely_benign	0.057	benign	-0.864	Destabilizing	None	N	0.281	neutral	N	0.408512667	None	None	N
L/W	0.1854	likely_benign	0.1791	benign	-1.004	Destabilizing	0.958	D	0.481	neutral	None	None	None	None	N
L/Y	0.2197	likely_benign	0.1932	benign	-0.794	Destabilizing	0.004	N	0.312	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.