TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23731	71416;71417;71418	chr2:178574941;178574940;178574939	chr2:179439668;179439667;179439666
N2AB	22090	66493;66494;66495	chr2:178574941;178574940;178574939	chr2:179439668;179439667;179439666
N2A	21163	63712;63713;63714	chr2:178574941;178574940;178574939	chr2:179439668;179439667;179439666
N2B	14666	44221;44222;44223	chr2:178574941;178574940;178574939	chr2:179439668;179439667;179439666
Novex-1	14791	44596;44597;44598	chr2:178574941;178574940;178574939	chr2:179439668;179439667;179439666
Novex-2	14858	44797;44798;44799	chr2:178574941;178574940;178574939	chr2:179439668;179439667;179439666
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-60
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.2235
• 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	None	None	0.549	N	0.543	0.13	0.156986980423	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.0754	likely_benign	0.077	benign	-0.734	Destabilizing	0.201	N	0.531	neutral	N	0.444452685	None	None	N
T/C	0.2456	likely_benign	0.268	benign	-0.41	Destabilizing	0.992	D	0.568	neutral	None	None	None	None	N
T/D	0.4477	ambiguous	0.4576	ambiguous	-0.457	Destabilizing	0.85	D	0.569	neutral	None	None	None	None	N
T/E	0.2381	likely_benign	0.2577	benign	-0.426	Destabilizing	0.447	N	0.55	neutral	None	None	None	None	N
T/F	0.272	likely_benign	0.277	benign	-0.63	Destabilizing	0.92	D	0.603	neutral	None	None	None	None	N
T/G	0.2024	likely_benign	0.2113	benign	-1.038	Destabilizing	0.617	D	0.581	neutral	None	None	None	None	N
T/H	0.2094	likely_benign	0.2267	benign	-1.39	Destabilizing	0.992	D	0.619	neutral	None	None	None	None	N
T/I	0.1084	likely_benign	0.1162	benign	-0.005	Destabilizing	0.036	N	0.405	neutral	N	0.506058504	None	None	N
T/K	0.0804	likely_benign	0.0911	benign	-0.914	Destabilizing	0.005	N	0.337	neutral	None	None	None	None	N
T/L	0.0853	likely_benign	0.0938	benign	-0.005	Destabilizing	0.447	N	0.547	neutral	None	None	None	None	N
T/M	0.0881	likely_benign	0.0899	benign	0.213	Stabilizing	0.92	D	0.557	neutral	None	None	None	None	N
T/N	0.1434	likely_benign	0.1472	benign	-0.868	Destabilizing	0.81	D	0.549	neutral	N	0.496497658	None	None	N
T/P	0.4557	ambiguous	0.4389	ambiguous	-0.214	Destabilizing	0.004	N	0.389	neutral	N	0.444799402	None	None	N
T/Q	0.1429	likely_benign	0.1611	benign	-0.922	Destabilizing	0.85	D	0.565	neutral	None	None	None	None	N
T/R	0.082	likely_benign	0.0861	benign	-0.794	Destabilizing	0.739	D	0.571	neutral	None	None	None	None	N
T/S	0.1075	likely_benign	0.108	benign	-1.076	Destabilizing	0.549	D	0.543	neutral	N	0.434025048	None	None	N
T/V	0.0816	likely_benign	0.0869	benign	-0.214	Destabilizing	0.447	N	0.533	neutral	None	None	None	None	N
T/W	0.6449	likely_pathogenic	0.6297	pathogenic	-0.653	Destabilizing	0.992	D	0.685	prob.neutral	None	None	None	None	N
T/Y	0.3048	likely_benign	0.3248	benign	-0.422	Destabilizing	0.972	D	0.609	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.