TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8407	25444;25445;25446	chr2:178717655;178717654;178717653	chr2:179582382;179582381;179582380
N2AB	8090	24493;24494;24495	chr2:178717655;178717654;178717653	chr2:179582382;179582381;179582380
N2A	7163	21712;21713;21714	chr2:178717655;178717654;178717653	chr2:179582382;179582381;179582380
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-69
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.2263
• 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
Q/H	rs1381783502	None	0.997	N	0.426	0.303	0.199424873507	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Q/H	rs1381783502	None	0.997	N	0.426	0.303	0.199424873507	gnomAD-4.0.0	3.84524E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.18233E-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
Q/A	0.4413	ambiguous	0.4651	ambiguous	-0.449	Destabilizing	0.843	D	0.333	neutral	None	None	None	None	I
Q/C	0.8116	likely_pathogenic	0.841	pathogenic	-0.116	Destabilizing	0.999	D	0.505	neutral	None	None	None	None	I
Q/D	0.6512	likely_pathogenic	0.6922	pathogenic	-1.312	Destabilizing	0.787	D	0.285	neutral	None	None	None	None	I
Q/E	0.1323	likely_benign	0.1355	benign	-1.212	Destabilizing	0.095	N	0.134	neutral	N	0.493077004	None	None	I
Q/F	0.7827	likely_pathogenic	0.8203	pathogenic	-0.365	Destabilizing	0.996	D	0.517	neutral	None	None	None	None	I
Q/G	0.5419	ambiguous	0.5869	pathogenic	-0.794	Destabilizing	0.961	D	0.423	neutral	None	None	None	None	I
Q/H	0.272	likely_benign	0.3057	benign	-0.911	Destabilizing	0.997	D	0.426	neutral	N	0.516724655	None	None	I
Q/I	0.5249	ambiguous	0.5554	ambiguous	0.423	Stabilizing	0.922	D	0.5	neutral	None	None	None	None	I
Q/K	0.1133	likely_benign	0.1238	benign	-0.311	Destabilizing	0.881	D	0.351	neutral	N	0.483244012	None	None	I
Q/L	0.2265	likely_benign	0.2541	benign	0.423	Stabilizing	0.787	D	0.419	neutral	N	0.51620458	None	None	I
Q/M	0.5244	ambiguous	0.544	ambiguous	0.916	Stabilizing	0.994	D	0.412	neutral	None	None	None	None	I
Q/N	0.4965	ambiguous	0.5269	ambiguous	-0.971	Destabilizing	0.947	D	0.285	neutral	None	None	None	None	I
Q/P	0.7131	likely_pathogenic	0.7768	pathogenic	0.164	Stabilizing	0.965	D	0.501	neutral	N	0.508471527	None	None	I
Q/R	0.1224	likely_benign	0.1394	benign	-0.287	Destabilizing	0.922	D	0.3	neutral	N	0.487785827	None	None	I
Q/S	0.464	ambiguous	0.4973	ambiguous	-0.973	Destabilizing	0.494	N	0.115	neutral	None	None	None	None	I
Q/T	0.3679	ambiguous	0.3889	ambiguous	-0.689	Destabilizing	0.013	N	0.215	neutral	None	None	None	None	I
Q/V	0.3782	ambiguous	0.4032	ambiguous	0.164	Stabilizing	0.087	N	0.336	neutral	None	None	None	None	I
Q/W	0.6827	likely_pathogenic	0.7345	pathogenic	-0.348	Destabilizing	1.0	D	0.513	neutral	None	None	None	None	I
Q/Y	0.5823	likely_pathogenic	0.6337	pathogenic	-0.013	Destabilizing	0.999	D	0.481	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.