TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13973	42142;42143;42144	chr2:178635272;178635271;178635270	chr2:179499999;179499998;179499997
N2AB	12332	37219;37220;37221	chr2:178635272;178635271;178635270	chr2:179499999;179499998;179499997
N2A	11405	34438;34439;34440	chr2:178635272;178635271;178635270	chr2:179499999;179499998;179499997
N2B	4908	14947;14948;14949	chr2:178635272;178635271;178635270	chr2:179499999;179499998;179499997
Novex-1	5033	15322;15323;15324	chr2:178635272;178635271;178635270	chr2:179499999;179499998;179499997
Novex-2	5100	15523;15524;15525	chr2:178635272;178635271;178635270	chr2:179499999;179499998;179499997
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-90
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5229
• 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
D/G	None	None	0.015	N	0.322	0.222	0.159798565429	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
D/N	None	None	0.919	N	0.541	0.193	0.167679373172	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.9015	likely_pathogenic	0.8177	pathogenic	-0.216	Destabilizing	0.702	D	0.553	neutral	N	0.502602284	None	None	N
D/C	0.9965	likely_pathogenic	0.9921	pathogenic	-0.08	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
D/E	0.8853	likely_pathogenic	0.8045	pathogenic	-0.326	Destabilizing	0.923	D	0.544	neutral	N	0.5000786	None	None	N
D/F	0.9972	likely_pathogenic	0.9944	pathogenic	0.003	Stabilizing	0.997	D	0.787	deleterious	None	None	None	None	N
D/G	0.8659	likely_pathogenic	0.7718	pathogenic	-0.441	Destabilizing	0.015	N	0.322	neutral	N	0.423589755	None	None	N
D/H	0.9696	likely_pathogenic	0.9336	pathogenic	0.199	Stabilizing	0.999	D	0.623	neutral	N	0.504458443	None	None	N
D/I	0.9947	likely_pathogenic	0.9872	pathogenic	0.337	Stabilizing	0.991	D	0.785	deleterious	None	None	None	None	N
D/K	0.9878	likely_pathogenic	0.9724	pathogenic	0.321	Stabilizing	0.938	D	0.658	prob.neutral	None	None	None	None	N
D/L	0.9909	likely_pathogenic	0.9824	pathogenic	0.337	Stabilizing	0.991	D	0.669	prob.neutral	None	None	None	None	N
D/M	0.9964	likely_pathogenic	0.9909	pathogenic	0.344	Stabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
D/N	0.4387	ambiguous	0.2943	benign	-0.124	Destabilizing	0.919	D	0.541	neutral	N	0.431191681	None	None	N
D/P	0.9594	likely_pathogenic	0.9275	pathogenic	0.176	Stabilizing	0.991	D	0.631	neutral	None	None	None	None	N
D/Q	0.9885	likely_pathogenic	0.9696	pathogenic	-0.056	Destabilizing	0.991	D	0.578	neutral	None	None	None	None	N
D/R	0.993	likely_pathogenic	0.9834	pathogenic	0.548	Stabilizing	0.991	D	0.788	deleterious	None	None	None	None	N
D/S	0.754	likely_pathogenic	0.5971	pathogenic	-0.213	Destabilizing	0.198	N	0.112	neutral	None	None	None	None	N
D/T	0.9507	likely_pathogenic	0.8992	pathogenic	-0.029	Destabilizing	0.883	D	0.535	neutral	None	None	None	None	N
D/V	0.9812	likely_pathogenic	0.9597	pathogenic	0.176	Stabilizing	0.988	D	0.68	prob.neutral	N	0.505072902	None	None	N
D/W	0.9995	likely_pathogenic	0.9987	pathogenic	0.164	Stabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
D/Y	0.9745	likely_pathogenic	0.9437	pathogenic	0.253	Stabilizing	0.996	D	0.778	deleterious	N	0.506116766	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.