TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6213	18862;18863;18864	chr2:178729519;178729518;178729517	chr2:179594246;179594245;179594244
N2AB	5896	17911;17912;17913	chr2:178729519;178729518;178729517	chr2:179594246;179594245;179594244
N2A	4969	15130;15131;15132	chr2:178729519;178729518;178729517	chr2:179594246;179594245;179594244
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-46
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.9084
• 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
Y/C	rs1489995255	None	0.008	N	0.37	0.123	0.499665682712	gnomAD-4.0.0	1.59189E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41896E-04	0	0	0
Y/F	rs1489995255	0.004	None	N	0.27	0.129	0.335661160332	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
Y/F	rs1489995255	0.004	None	N	0.27	0.129	0.335661160332	gnomAD-4.0.0	1.59189E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43312E-05	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
Y/A	0.1054	likely_benign	0.1283	benign	-0.801	Destabilizing	None	N	0.225	neutral	None	None	None	None	N
Y/C	0.1169	likely_benign	0.1331	benign	0.137	Stabilizing	0.008	N	0.37	neutral	N	0.43048975	None	None	N
Y/D	0.0483	likely_benign	0.0512	benign	0.606	Stabilizing	None	N	0.258	neutral	N	0.309256837	None	None	N
Y/E	0.1333	likely_benign	0.1658	benign	0.597	Stabilizing	None	N	0.231	neutral	None	None	None	None	N
Y/F	0.0905	likely_benign	0.1005	benign	-0.39	Destabilizing	None	N	0.27	neutral	N	0.400860276	None	None	N
Y/G	0.0791	likely_benign	0.0782	benign	-1.013	Destabilizing	None	N	0.258	neutral	None	None	None	None	N
Y/H	0.1116	likely_benign	0.118	benign	0.031	Stabilizing	0.001	N	0.293	neutral	N	0.374116392	None	None	N
Y/I	0.181	likely_benign	0.2178	benign	-0.248	Destabilizing	None	N	0.262	neutral	None	None	None	None	N
Y/K	0.2455	likely_benign	0.2572	benign	0.083	Stabilizing	None	N	0.238	neutral	None	None	None	None	N
Y/L	0.1855	likely_benign	0.2174	benign	-0.248	Destabilizing	None	N	0.255	neutral	None	None	None	None	N
Y/M	0.265	likely_benign	0.3061	benign	-0.111	Destabilizing	0.01	N	0.38	neutral	None	None	None	None	N
Y/N	0.0377	likely_benign	0.038	benign	-0.092	Destabilizing	None	N	0.235	neutral	N	0.332845773	None	None	N
Y/P	0.4822	ambiguous	0.5174	ambiguous	-0.414	Destabilizing	None	N	0.276	neutral	None	None	None	None	N
Y/Q	0.1779	likely_benign	0.2058	benign	-0.045	Destabilizing	None	N	0.262	neutral	None	None	None	None	N
Y/R	0.2297	likely_benign	0.2275	benign	0.325	Stabilizing	None	N	0.243	neutral	None	None	None	None	N
Y/S	0.06	likely_benign	0.065	benign	-0.477	Destabilizing	None	N	0.229	neutral	N	0.333904565	None	None	N
Y/T	0.1075	likely_benign	0.1344	benign	-0.391	Destabilizing	None	N	0.225	neutral	None	None	None	None	N
Y/V	0.1341	likely_benign	0.1536	benign	-0.414	Destabilizing	None	N	0.251	neutral	None	None	None	None	N
Y/W	0.3978	ambiguous	0.4264	ambiguous	-0.481	Destabilizing	0.051	N	0.383	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.