TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23796	71611;71612;71613	chr2:178574746;178574745;178574744	chr2:179439473;179439472;179439471
N2AB	22155	66688;66689;66690	chr2:178574746;178574745;178574744	chr2:179439473;179439472;179439471
N2A	21228	63907;63908;63909	chr2:178574746;178574745;178574744	chr2:179439473;179439472;179439471
N2B	14731	44416;44417;44418	chr2:178574746;178574745;178574744	chr2:179439473;179439472;179439471
Novex-1	14856	44791;44792;44793	chr2:178574746;178574745;178574744	chr2:179439473;179439472;179439471
Novex-2	14923	44992;44993;44994	chr2:178574746;178574745;178574744	chr2:179439473;179439472;179439471
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: Fn3-60
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3208
• 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/D	rs878854330	None	0.008	N	0.151	0.079	0.12205267543	gnomAD-4.0.0	1.59336E-06	None	None	None	None	N	None	5.66059E-05	0	None	0	0	None	0	0	0	0	0
E/V	None	None	0.949	N	0.719	0.459	0.566737540366	gnomAD-4.0.0	1.59334E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8618E-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	0.2212	likely_benign	0.2262	benign	-1.006	Destabilizing	0.722	D	0.564	neutral	N	0.475700879	None	None	N
E/C	0.8855	likely_pathogenic	0.8868	pathogenic	-0.559	Destabilizing	0.996	D	0.786	deleterious	None	None	None	None	N
E/D	0.4513	ambiguous	0.4574	ambiguous	-1.186	Destabilizing	0.008	N	0.151	neutral	N	0.472066801	None	None	N
E/F	0.9339	likely_pathogenic	0.927	pathogenic	-0.449	Destabilizing	0.987	D	0.791	deleterious	None	None	None	None	N
E/G	0.3864	ambiguous	0.3869	ambiguous	-1.399	Destabilizing	0.722	D	0.642	neutral	N	0.485513475	None	None	N
E/H	0.7351	likely_pathogenic	0.7169	pathogenic	-0.798	Destabilizing	0.961	D	0.598	neutral	None	None	None	None	N
E/I	0.5946	likely_pathogenic	0.6195	pathogenic	0.077	Stabilizing	0.961	D	0.795	deleterious	None	None	None	None	N
E/K	0.3541	ambiguous	0.3632	ambiguous	-0.855	Destabilizing	0.565	D	0.503	neutral	N	0.509264673	None	None	N
E/L	0.5978	likely_pathogenic	0.6074	pathogenic	0.077	Stabilizing	0.923	D	0.725	prob.delet.	None	None	None	None	N
E/M	0.6274	likely_pathogenic	0.6334	pathogenic	0.617	Stabilizing	0.996	D	0.774	deleterious	None	None	None	None	N
E/N	0.5432	ambiguous	0.5301	ambiguous	-1.293	Destabilizing	0.633	D	0.535	neutral	None	None	None	None	N
E/P	0.5563	ambiguous	0.5182	ambiguous	-0.263	Destabilizing	0.961	D	0.715	prob.delet.	None	None	None	None	N
E/Q	0.1557	likely_benign	0.1474	benign	-1.128	Destabilizing	0.092	N	0.15	neutral	D	0.525311561	None	None	N
E/R	0.4899	ambiguous	0.4811	ambiguous	-0.609	Destabilizing	0.775	D	0.54	neutral	None	None	None	None	N
E/S	0.3358	likely_benign	0.3354	benign	-1.683	Destabilizing	0.775	D	0.464	neutral	None	None	None	None	N
E/T	0.3735	ambiguous	0.3772	ambiguous	-1.352	Destabilizing	0.775	D	0.651	neutral	None	None	None	None	N
E/V	0.3848	ambiguous	0.4019	ambiguous	-0.263	Destabilizing	0.949	D	0.719	prob.delet.	N	0.474246075	None	None	N
E/W	0.9827	likely_pathogenic	0.9796	pathogenic	-0.22	Destabilizing	0.996	D	0.765	deleterious	None	None	None	None	N
E/Y	0.875	likely_pathogenic	0.8616	pathogenic	-0.205	Destabilizing	0.987	D	0.788	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.