TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5252	15979;15980;15981	chr2:178733635;178733634;178733633	chr2:179598362;179598361;179598360
N2AB	4935	15028;15029;15030	chr2:178733635;178733634;178733633	chr2:179598362;179598361;179598360
N2A	4008	12247;12248;12249	chr2:178733635;178733634;178733633	chr2:179598362;179598361;179598360
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-35
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.3633
• 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
V/F	None	None	0.001	N	0.212	0.201	0.312608672186	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	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
V/A	0.0899	likely_benign	0.0918	benign	-0.596	Destabilizing	0.047	N	0.239	neutral	N	0.479725794	None	None	N
V/C	0.5601	ambiguous	0.6014	pathogenic	-0.628	Destabilizing	0.983	D	0.555	neutral	None	None	None	None	N
V/D	0.2094	likely_benign	0.2206	benign	-0.077	Destabilizing	0.101	N	0.501	neutral	N	0.471594416	None	None	N
V/E	0.1569	likely_benign	0.1622	benign	-0.178	Destabilizing	0.004	N	0.334	neutral	None	None	None	None	N
V/F	0.0928	likely_benign	0.0972	benign	-0.796	Destabilizing	0.001	N	0.212	neutral	N	0.404807557	None	None	N
V/G	0.1481	likely_benign	0.1576	benign	-0.755	Destabilizing	0.183	N	0.493	neutral	N	0.505851624	None	None	N
V/H	0.2997	likely_benign	0.3293	benign	-0.381	Destabilizing	0.94	D	0.573	neutral	None	None	None	None	N
V/I	0.0688	likely_benign	0.0703	benign	-0.321	Destabilizing	0.001	N	0.157	neutral	N	0.49465076	None	None	N
V/K	0.2072	likely_benign	0.2167	benign	-0.316	Destabilizing	0.418	N	0.527	neutral	None	None	None	None	N
V/L	0.1316	likely_benign	0.1372	benign	-0.321	Destabilizing	0.017	N	0.243	neutral	N	0.48891841	None	None	N
V/M	0.0901	likely_benign	0.0965	benign	-0.267	Destabilizing	0.716	D	0.522	neutral	None	None	None	None	N
V/N	0.1481	likely_benign	0.1548	benign	-0.042	Destabilizing	0.418	N	0.615	neutral	None	None	None	None	N
V/P	0.5369	ambiguous	0.5943	pathogenic	-0.376	Destabilizing	0.836	D	0.64	neutral	None	None	None	None	N
V/Q	0.1792	likely_benign	0.187	benign	-0.297	Destabilizing	0.418	N	0.629	neutral	None	None	None	None	N
V/R	0.1786	likely_benign	0.1795	benign	0.129	Stabilizing	0.418	N	0.641	neutral	None	None	None	None	N
V/S	0.0966	likely_benign	0.1021	benign	-0.498	Destabilizing	0.027	N	0.362	neutral	None	None	None	None	N
V/T	0.0845	likely_benign	0.0908	benign	-0.495	Destabilizing	0.129	N	0.372	neutral	None	None	None	None	N
V/W	0.5227	ambiguous	0.5645	pathogenic	-0.858	Destabilizing	0.983	D	0.571	neutral	None	None	None	None	N
V/Y	0.3055	likely_benign	0.3298	benign	-0.529	Destabilizing	0.264	N	0.516	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.