TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17338	52237;52238;52239	chr2:178609298;178609297;178609296	chr2:179474025;179474024;179474023
N2AB	15697	47314;47315;47316	chr2:178609298;178609297;178609296	chr2:179474025;179474024;179474023
N2A	14770	44533;44534;44535	chr2:178609298;178609297;178609296	chr2:179474025;179474024;179474023
N2B	8273	25042;25043;25044	chr2:178609298;178609297;178609296	chr2:179474025;179474024;179474023
Novex-1	8398	25417;25418;25419	chr2:178609298;178609297;178609296	chr2:179474025;179474024;179474023
Novex-2	8465	25618;25619;25620	chr2:178609298;178609297;178609296	chr2:179474025;179474024;179474023
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-112
• Domain position: 88
• Structural Position: 143
• Q(SASA): 0.4406
• 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/H	None	None	1.0	N	0.753	0.359	0.20549828249	gnomAD-4.0.0	1.62489E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.9099E-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	0.4377	ambiguous	0.4632	ambiguous	-0.466	Destabilizing	0.984	D	0.642	neutral	N	0.50436778	None	None	N
D/C	0.8279	likely_pathogenic	0.8476	pathogenic	-0.03	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
D/E	0.2454	likely_benign	0.2645	benign	-0.455	Destabilizing	0.999	D	0.454	neutral	N	0.488416893	None	None	N
D/F	0.7922	likely_pathogenic	0.8191	pathogenic	-0.357	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
D/G	0.3368	likely_benign	0.3347	benign	-0.695	Destabilizing	0.275	N	0.357	neutral	N	0.480682844	None	None	N
D/H	0.5847	likely_pathogenic	0.5769	pathogenic	-0.354	Destabilizing	1.0	D	0.753	deleterious	N	0.501655549	None	None	N
D/I	0.8099	likely_pathogenic	0.8395	pathogenic	0.102	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
D/K	0.7149	likely_pathogenic	0.6963	pathogenic	0.193	Stabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
D/L	0.7202	likely_pathogenic	0.7447	pathogenic	0.102	Stabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
D/M	0.8728	likely_pathogenic	0.8965	pathogenic	0.367	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
D/N	0.1948	likely_benign	0.2057	benign	-0.191	Destabilizing	0.999	D	0.687	prob.neutral	N	0.45782184	None	None	N
D/P	0.9527	likely_pathogenic	0.9462	pathogenic	-0.065	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
D/Q	0.597	likely_pathogenic	0.5962	pathogenic	-0.146	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
D/R	0.7493	likely_pathogenic	0.7297	pathogenic	0.323	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
D/S	0.3167	likely_benign	0.3294	benign	-0.305	Destabilizing	0.994	D	0.621	neutral	None	None	None	None	N
D/T	0.6128	likely_pathogenic	0.6497	pathogenic	-0.119	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
D/V	0.6319	likely_pathogenic	0.6637	pathogenic	-0.065	Destabilizing	1.0	D	0.775	deleterious	N	0.458480499	None	None	N
D/W	0.9517	likely_pathogenic	0.9569	pathogenic	-0.187	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
D/Y	0.3957	ambiguous	0.4007	ambiguous	-0.112	Destabilizing	1.0	D	0.784	deleterious	N	0.458227009	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.