TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5499	16720;16721;16722	chr2:178732566;178732565;178732564	chr2:179597293;179597292;179597291
N2AB	5182	15769;15770;15771	chr2:178732566;178732565;178732564	chr2:179597293;179597292;179597291
N2A	4255	12988;12989;12990	chr2:178732566;178732565;178732564	chr2:179597293;179597292;179597291
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-38
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.2553
• 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
T/S	rs774316553	-1.261	0.005	N	0.279	0.141	0.177238962908	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
T/S	rs774316553	-1.261	0.005	N	0.279	0.141	0.177238962908	gnomAD-4.0.0	1.59156E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8586E-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
T/A	0.0827	likely_benign	0.0777	benign	-0.813	Destabilizing	None	N	0.131	neutral	N	0.494194512	None	None	N
T/C	0.3753	ambiguous	0.3575	ambiguous	-0.437	Destabilizing	0.628	D	0.377	neutral	None	None	None	None	N
T/D	0.3283	likely_benign	0.3676	ambiguous	-0.349	Destabilizing	0.038	N	0.369	neutral	None	None	None	None	N
T/E	0.2236	likely_benign	0.2668	benign	-0.369	Destabilizing	0.016	N	0.335	neutral	None	None	None	None	N
T/F	0.1791	likely_benign	0.1856	benign	-0.98	Destabilizing	0.038	N	0.423	neutral	None	None	None	None	N
T/G	0.213	likely_benign	0.2006	benign	-1.047	Destabilizing	0.016	N	0.315	neutral	None	None	None	None	N
T/H	0.1737	likely_benign	0.1731	benign	-1.356	Destabilizing	0.214	N	0.451	neutral	None	None	None	None	N
T/I	0.1428	likely_benign	0.1648	benign	-0.286	Destabilizing	0.029	N	0.369	neutral	N	0.500064478	None	None	N
T/K	0.1356	likely_benign	0.1471	benign	-0.716	Destabilizing	None	N	0.147	neutral	None	None	None	None	N
T/L	0.0888	likely_benign	0.0925	benign	-0.286	Destabilizing	0.002	N	0.317	neutral	None	None	None	None	N
T/M	0.0873	likely_benign	0.0929	benign	0.137	Stabilizing	0.003	N	0.26	neutral	None	None	None	None	N
T/N	0.1068	likely_benign	0.1036	benign	-0.592	Destabilizing	None	N	0.141	neutral	N	0.506643734	None	None	N
T/P	0.2888	likely_benign	0.3368	benign	-0.431	Destabilizing	0.106	N	0.369	neutral	D	0.531406106	None	None	N
T/Q	0.1502	likely_benign	0.1626	benign	-0.836	Destabilizing	0.072	N	0.35	neutral	None	None	None	None	N
T/R	0.0983	likely_benign	0.1029	benign	-0.419	Destabilizing	0.038	N	0.365	neutral	None	None	None	None	N
T/S	0.098	likely_benign	0.0921	benign	-0.859	Destabilizing	0.005	N	0.279	neutral	N	0.415829729	None	None	N
T/V	0.1284	likely_benign	0.1365	benign	-0.431	Destabilizing	0.016	N	0.254	neutral	None	None	None	None	N
T/W	0.3847	ambiguous	0.4168	ambiguous	-0.891	Destabilizing	0.676	D	0.417	neutral	None	None	None	None	N
T/Y	0.1964	likely_benign	0.2029	benign	-0.666	Destabilizing	None	N	0.288	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.