TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15820	47683;47684;47685	chr2:178617893;178617892;178617891	chr2:179482620;179482619;179482618
N2AB	14179	42760;42761;42762	chr2:178617893;178617892;178617891	chr2:179482620;179482619;179482618
N2A	13252	39979;39980;39981	chr2:178617893;178617892;178617891	chr2:179482620;179482619;179482618
N2B	6755	20488;20489;20490	chr2:178617893;178617892;178617891	chr2:179482620;179482619;179482618
Novex-1	6880	20863;20864;20865	chr2:178617893;178617892;178617891	chr2:179482620;179482619;179482618
Novex-2	6947	21064;21065;21066	chr2:178617893;178617892;178617891	chr2:179482620;179482619;179482618
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-2
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.2435
• 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/G	None	None	0.97	D	0.822	0.579	0.904401613803	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
V/L	rs1553710237	None	0.006	N	0.237	0.065	0.30212335484	gnomAD-4.0.0	1.5935E-06	None	None	None	None	N	None	5.67924E-05	0	None	0	0	None	0	0	0	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	0.714	likely_pathogenic	0.6709	pathogenic	-1.93	Destabilizing	0.656	D	0.691	prob.neutral	N	0.487132597	None	None	N
V/C	0.9185	likely_pathogenic	0.8979	pathogenic	-1.689	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
V/D	0.9863	likely_pathogenic	0.9825	pathogenic	-1.713	Destabilizing	0.99	D	0.842	deleterious	D	0.575599795	None	None	N
V/E	0.9571	likely_pathogenic	0.9457	pathogenic	-1.554	Destabilizing	0.993	D	0.815	deleterious	None	None	None	None	N
V/F	0.4768	ambiguous	0.4182	ambiguous	-1.223	Destabilizing	0.942	D	0.791	deleterious	D	0.562337202	None	None	N
V/G	0.9125	likely_pathogenic	0.8835	pathogenic	-2.426	Highly Destabilizing	0.97	D	0.822	deleterious	D	0.690785447	None	None	N
V/H	0.9801	likely_pathogenic	0.9733	pathogenic	-1.978	Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	N
V/I	0.0805	likely_benign	0.0804	benign	-0.588	Destabilizing	0.006	N	0.19	neutral	N	0.472748129	None	None	N
V/K	0.9607	likely_pathogenic	0.9453	pathogenic	-1.584	Destabilizing	0.978	D	0.821	deleterious	None	None	None	None	N
V/L	0.2406	likely_benign	0.3384	benign	-0.588	Destabilizing	0.006	N	0.237	neutral	N	0.470694856	None	None	N
V/M	0.3025	likely_benign	0.2576	benign	-0.687	Destabilizing	0.956	D	0.705	prob.neutral	None	None	None	None	N
V/N	0.9617	likely_pathogenic	0.9524	pathogenic	-1.696	Destabilizing	0.993	D	0.839	deleterious	None	None	None	None	N
V/P	0.977	likely_pathogenic	0.9704	pathogenic	-1.004	Destabilizing	0.993	D	0.811	deleterious	None	None	None	None	N
V/Q	0.9512	likely_pathogenic	0.9339	pathogenic	-1.605	Destabilizing	0.993	D	0.802	deleterious	None	None	None	None	N
V/R	0.9453	likely_pathogenic	0.9263	pathogenic	-1.364	Destabilizing	0.978	D	0.837	deleterious	None	None	None	None	N
V/S	0.9203	likely_pathogenic	0.9025	pathogenic	-2.414	Highly Destabilizing	0.978	D	0.815	deleterious	None	None	None	None	N
V/T	0.8439	likely_pathogenic	0.814	pathogenic	-2.092	Highly Destabilizing	0.86	D	0.723	prob.delet.	None	None	None	None	N
V/W	0.9813	likely_pathogenic	0.9705	pathogenic	-1.513	Destabilizing	0.998	D	0.828	deleterious	None	None	None	None	N
V/Y	0.9224	likely_pathogenic	0.8961	pathogenic	-1.18	Destabilizing	0.978	D	0.778	deleterious	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.