TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19718	59377;59378;59379	chr2:178592967;178592966;178592965	chr2:179457694;179457693;179457692
N2AB	18077	54454;54455;54456	chr2:178592967;178592966;178592965	chr2:179457694;179457693;179457692
N2A	17150	51673;51674;51675	chr2:178592967;178592966;178592965	chr2:179457694;179457693;179457692
N2B	10653	32182;32183;32184	chr2:178592967;178592966;178592965	chr2:179457694;179457693;179457692
Novex-1	10778	32557;32558;32559	chr2:178592967;178592966;178592965	chr2:179457694;179457693;179457692
Novex-2	10845	32758;32759;32760	chr2:178592967;178592966;178592965	chr2:179457694;179457693;179457692
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-31
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.142
• 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
E/K	None	None	0.992	D	0.664	0.397	0.359151904892	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
E/A	0.7108	likely_pathogenic	0.7418	pathogenic	-1.071	Destabilizing	0.998	D	0.633	neutral	D	0.528443481	None	None	N
E/C	0.9584	likely_pathogenic	0.9671	pathogenic	-0.334	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/D	0.6645	likely_pathogenic	0.7297	pathogenic	-1.771	Destabilizing	0.998	D	0.634	neutral	N	0.486398848	None	None	N
E/F	0.9569	likely_pathogenic	0.9765	pathogenic	-0.757	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/G	0.8639	likely_pathogenic	0.8811	pathogenic	-1.46	Destabilizing	0.999	D	0.723	prob.delet.	D	0.536965857	None	None	N
E/H	0.9196	likely_pathogenic	0.9448	pathogenic	-0.638	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/I	0.8821	likely_pathogenic	0.9201	pathogenic	0.044	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/K	0.8912	likely_pathogenic	0.9026	pathogenic	-1.101	Destabilizing	0.992	D	0.664	neutral	D	0.522403093	None	None	N
E/L	0.9063	likely_pathogenic	0.9352	pathogenic	0.044	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/M	0.8623	likely_pathogenic	0.9022	pathogenic	0.682	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/N	0.8998	likely_pathogenic	0.9316	pathogenic	-1.415	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/P	0.9991	likely_pathogenic	0.9992	pathogenic	-0.313	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Q	0.4685	ambiguous	0.5061	ambiguous	-1.103	Destabilizing	0.998	D	0.709	prob.delet.	N	0.475318804	None	None	N
E/R	0.9191	likely_pathogenic	0.9256	pathogenic	-1.025	Destabilizing	0.91	D	0.386	neutral	None	None	None	None	N
E/S	0.7634	likely_pathogenic	0.8071	pathogenic	-1.954	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
E/T	0.8604	likely_pathogenic	0.8928	pathogenic	-1.58	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/V	0.7858	likely_pathogenic	0.8428	pathogenic	-0.313	Destabilizing	0.999	D	0.75	deleterious	N	0.517847644	None	None	N
E/W	0.9836	likely_pathogenic	0.9902	pathogenic	-0.918	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/Y	0.9174	likely_pathogenic	0.9533	pathogenic	-0.572	Destabilizing	1.0	D	0.801	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.