TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8974	27145;27146;27147	chr2:178713214;178713213;178713212	chr2:179577941;179577940;179577939
N2AB	8657	26194;26195;26196	chr2:178713214;178713213;178713212	chr2:179577941;179577940;179577939
N2A	7730	23413;23414;23415	chr2:178713214;178713213;178713212	chr2:179577941;179577940;179577939
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-75
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.6043
• 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
T/A	None	None	None	N	0.093	0.121	0.136095386433	gnomAD-4.0.0	1.59168E-06	None	None	None	None	I	None	0	0	None	0	2.77469E-05	None	0	0	0	0	0
T/I	rs1176692583	0.067	None	N	0.245	0.118	0.260249123532	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs1176692583	0.067	None	N	0.245	0.118	0.260249123532	gnomAD-4.0.0	2.03005E-06	None	None	None	None	I	None	3.49614E-05	0	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
T/A	0.0722	likely_benign	0.0706	benign	-1.307	Destabilizing	None	N	0.093	neutral	N	0.510507971	None	None	I
T/C	0.3439	ambiguous	0.3782	ambiguous	-0.831	Destabilizing	0.356	N	0.541	neutral	None	None	None	None	I
T/D	0.4338	ambiguous	0.4896	ambiguous	-0.439	Destabilizing	0.072	N	0.543	neutral	None	None	None	None	I
T/E	0.3149	likely_benign	0.3494	ambiguous	-0.392	Destabilizing	0.072	N	0.487	neutral	None	None	None	None	I
T/F	0.2002	likely_benign	0.2312	benign	-1.424	Destabilizing	0.214	N	0.591	neutral	None	None	None	None	I
T/G	0.249	likely_benign	0.2655	benign	-1.589	Destabilizing	0.016	N	0.447	neutral	None	None	None	None	I
T/H	0.238	likely_benign	0.2717	benign	-1.843	Destabilizing	0.628	D	0.533	neutral	None	None	None	None	I
T/I	0.1379	likely_benign	0.1473	benign	-0.625	Destabilizing	None	N	0.245	neutral	N	0.403665721	None	None	I
T/K	0.1868	likely_benign	0.2292	benign	-0.693	Destabilizing	0.072	N	0.489	neutral	None	None	None	None	I
T/L	0.0846	likely_benign	0.0869	benign	-0.625	Destabilizing	0.002	N	0.366	neutral	None	None	None	None	I
T/M	0.0695	likely_benign	0.0705	benign	-0.252	Destabilizing	0.002	N	0.354	neutral	None	None	None	None	I
T/N	0.1356	likely_benign	0.1609	benign	-0.789	Destabilizing	0.055	N	0.465	neutral	N	0.486960231	None	None	I
T/P	0.1447	likely_benign	0.1942	benign	-0.822	Destabilizing	None	N	0.377	neutral	N	0.505968943	None	None	I
T/Q	0.2211	likely_benign	0.2501	benign	-0.925	Destabilizing	0.356	N	0.592	neutral	None	None	None	None	I
T/R	0.1505	likely_benign	0.1841	benign	-0.554	Destabilizing	0.214	N	0.601	neutral	None	None	None	None	I
T/S	0.1149	likely_benign	0.123	benign	-1.156	Destabilizing	0.001	N	0.146	neutral	N	0.46746927	None	None	I
T/V	0.1184	likely_benign	0.112	benign	-0.822	Destabilizing	0.016	N	0.307	neutral	None	None	None	None	I
T/W	0.4929	ambiguous	0.5603	ambiguous	-1.289	Destabilizing	0.864	D	0.558	neutral	None	None	None	None	I
T/Y	0.1913	likely_benign	0.2309	benign	-1.048	Destabilizing	0.356	N	0.539	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.