TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19997	60214;60215;60216	chr2:178591830;178591829;178591828	chr2:179456557;179456556;179456555
N2AB	18356	55291;55292;55293	chr2:178591830;178591829;178591828	chr2:179456557;179456556;179456555
N2A	17429	52510;52511;52512	chr2:178591830;178591829;178591828	chr2:179456557;179456556;179456555
N2B	10932	33019;33020;33021	chr2:178591830;178591829;178591828	chr2:179456557;179456556;179456555
Novex-1	11057	33394;33395;33396	chr2:178591830;178591829;178591828	chr2:179456557;179456556;179456555
Novex-2	11124	33595;33596;33597	chr2:178591830;178591829;178591828	chr2:179456557;179456556;179456555
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-33
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.1786
• 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
V/F	None	None	0.989	N	0.539	0.278	0.673914265645	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.1437	likely_benign	0.142	benign	-1.779	Destabilizing	0.005	N	0.155	neutral	N	0.394939089	None	None	N
V/C	0.6288	likely_pathogenic	0.6591	pathogenic	-1.142	Destabilizing	0.998	D	0.543	neutral	None	None	None	None	N
V/D	0.4457	ambiguous	0.483	ambiguous	-2.651	Highly Destabilizing	0.801	D	0.593	neutral	N	0.460644006	None	None	N
V/E	0.2359	likely_benign	0.2558	benign	-2.473	Highly Destabilizing	0.728	D	0.455	neutral	None	None	None	None	N
V/F	0.1691	likely_benign	0.1771	benign	-1.12	Destabilizing	0.989	D	0.539	neutral	N	0.485849095	None	None	N
V/G	0.23	likely_benign	0.2433	benign	-2.255	Highly Destabilizing	0.669	D	0.497	neutral	N	0.455526188	None	None	N
V/H	0.4278	ambiguous	0.4444	ambiguous	-2.214	Highly Destabilizing	0.993	D	0.641	neutral	None	None	None	None	N
V/I	0.079	likely_benign	0.0794	benign	-0.468	Destabilizing	0.625	D	0.45	neutral	N	0.475074741	None	None	N
V/K	0.1913	likely_benign	0.2141	benign	-1.561	Destabilizing	0.728	D	0.487	neutral	None	None	None	None	N
V/L	0.1441	likely_benign	0.1578	benign	-0.468	Destabilizing	0.625	D	0.423	neutral	N	0.437844505	None	None	N
V/M	0.1371	likely_benign	0.1405	benign	-0.367	Destabilizing	0.991	D	0.527	neutral	None	None	None	None	N
V/N	0.274	likely_benign	0.2963	benign	-1.793	Destabilizing	0.974	D	0.609	neutral	None	None	None	None	N
V/P	0.9468	likely_pathogenic	0.9544	pathogenic	-0.877	Destabilizing	0.974	D	0.565	neutral	None	None	None	None	N
V/Q	0.189	likely_benign	0.2079	benign	-1.693	Destabilizing	0.172	N	0.394	neutral	None	None	None	None	N
V/R	0.1736	likely_benign	0.193	benign	-1.333	Destabilizing	0.949	D	0.61	neutral	None	None	None	None	N
V/S	0.1684	likely_benign	0.1728	benign	-2.281	Highly Destabilizing	0.728	D	0.452	neutral	None	None	None	None	N
V/T	0.1421	likely_benign	0.1409	benign	-1.987	Destabilizing	0.842	D	0.42	neutral	None	None	None	None	N
V/W	0.7856	likely_pathogenic	0.7933	pathogenic	-1.763	Destabilizing	0.998	D	0.689	prob.neutral	None	None	None	None	N
V/Y	0.4755	ambiguous	0.5004	ambiguous	-1.325	Destabilizing	0.991	D	0.541	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.