TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7783	23572;23573;23574	chr2:178720415;178720414;178720413	chr2:179585142;179585141;179585140
N2AB	7466	22621;22622;22623	chr2:178720415;178720414;178720413	chr2:179585142;179585141;179585140
N2A	6539	19840;19841;19842	chr2:178720415;178720414;178720413	chr2:179585142;179585141;179585140
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-62
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.2441
• 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
D/G	rs2078167222	None	0.862	N	0.527	0.432	0.329282125956	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
D/G	rs2078167222	None	0.862	N	0.527	0.432	0.329282125956	gnomAD-4.0.0	6.57065E-06	None	None	None	None	I	None	0	6.54793E-05	None	0	0	None	0	0	0	0	0
D/H	None	None	0.998	N	0.545	0.454	0.381071309025	gnomAD-4.0.0	1.59308E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86116E-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
D/A	0.3256	likely_benign	0.3304	benign	-0.755	Destabilizing	0.637	D	0.579	neutral	N	0.45334518	None	None	I
D/C	0.8472	likely_pathogenic	0.8441	pathogenic	-0.31	Destabilizing	0.005	N	0.423	neutral	None	None	None	None	I
D/E	0.5112	ambiguous	0.4974	ambiguous	-0.752	Destabilizing	0.006	N	0.146	neutral	N	0.510585329	None	None	I
D/F	0.9084	likely_pathogenic	0.9095	pathogenic	-0.417	Destabilizing	0.993	D	0.687	prob.neutral	None	None	None	None	I
D/G	0.407	ambiguous	0.3792	ambiguous	-1.101	Destabilizing	0.862	D	0.527	neutral	N	0.50393885	None	None	I
D/H	0.7186	likely_pathogenic	0.7355	pathogenic	-0.686	Destabilizing	0.998	D	0.545	neutral	N	0.50393885	None	None	I
D/I	0.7939	likely_pathogenic	0.8274	pathogenic	0.163	Stabilizing	0.385	N	0.47	neutral	None	None	None	None	I
D/K	0.8658	likely_pathogenic	0.8668	pathogenic	-0.458	Destabilizing	0.953	D	0.592	neutral	None	None	None	None	I
D/L	0.8381	likely_pathogenic	0.8511	pathogenic	0.163	Stabilizing	0.91	D	0.621	neutral	None	None	None	None	I
D/M	0.9237	likely_pathogenic	0.9278	pathogenic	0.645	Stabilizing	0.995	D	0.649	neutral	None	None	None	None	I
D/N	0.2356	likely_benign	0.2274	benign	-0.883	Destabilizing	0.794	D	0.547	neutral	N	0.502924892	None	None	I
D/P	0.9958	likely_pathogenic	0.9953	pathogenic	-0.118	Destabilizing	0.896	D	0.614	neutral	None	None	None	None	I
D/Q	0.7786	likely_pathogenic	0.7683	pathogenic	-0.766	Destabilizing	0.964	D	0.541	neutral	None	None	None	None	I
D/R	0.8739	likely_pathogenic	0.8737	pathogenic	-0.289	Destabilizing	0.986	D	0.679	prob.neutral	None	None	None	None	I
D/S	0.2119	likely_benign	0.2107	benign	-1.16	Destabilizing	0.849	D	0.458	neutral	None	None	None	None	I
D/T	0.5123	ambiguous	0.5211	ambiguous	-0.875	Destabilizing	0.836	D	0.556	neutral	None	None	None	None	I
D/V	0.5506	ambiguous	0.5893	pathogenic	-0.118	Destabilizing	0.572	D	0.625	neutral	N	0.473355093	None	None	I
D/W	0.9928	likely_pathogenic	0.9927	pathogenic	-0.218	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	I
D/Y	0.6896	likely_pathogenic	0.7186	pathogenic	-0.166	Destabilizing	0.997	D	0.669	neutral	D	0.524929941	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.