TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6299	19120;19121;19122	chr2:178729143;178729142;178729141	chr2:179593870;179593869;179593868
N2AB	5982	18169;18170;18171	chr2:178729143;178729142;178729141	chr2:179593870;179593869;179593868
N2A	5055	15388;15389;15390	chr2:178729143;178729142;178729141	chr2:179593870;179593869;179593868
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-47
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.7276
• Predicted PPI site: I

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/Q	rs2079911475	None	0.864	N	0.587	0.21	0.344710718752	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs2079911475	None	0.864	N	0.587	0.21	0.344710718752	gnomAD-4.0.0	1.88389E-06	None	None	None	None	I	None	2.69906E-05	0	None	0	0	None	0	0	0	0	1.6257E-05

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	0.1818	likely_benign	0.1895	benign	-0.26	Destabilizing	0.645	D	0.589	neutral	D	0.531384676	None	None	I
E/C	0.8715	likely_pathogenic	0.8962	pathogenic	-0.168	Destabilizing	0.995	D	0.721	prob.delet.	None	None	None	None	I
E/D	0.1593	likely_benign	0.1593	benign	-0.384	Destabilizing	0.006	N	0.256	neutral	N	0.498227631	None	None	I
E/F	0.7992	likely_pathogenic	0.8334	pathogenic	-0.047	Destabilizing	0.981	D	0.685	prob.neutral	None	None	None	None	I
E/G	0.1564	likely_benign	0.1724	benign	-0.455	Destabilizing	0.006	N	0.335	neutral	N	0.496279074	None	None	I
E/H	0.4853	ambiguous	0.5189	ambiguous	0.365	Stabilizing	0.995	D	0.605	neutral	None	None	None	None	I
E/I	0.4357	ambiguous	0.4542	ambiguous	0.221	Stabilizing	0.945	D	0.703	prob.neutral	None	None	None	None	I
E/K	0.1392	likely_benign	0.1467	benign	0.396	Stabilizing	0.645	D	0.586	neutral	D	0.525839996	None	None	I
E/L	0.4757	ambiguous	0.4905	ambiguous	0.221	Stabilizing	0.945	D	0.687	prob.neutral	None	None	None	None	I
E/M	0.5426	ambiguous	0.5686	pathogenic	0.134	Stabilizing	0.995	D	0.667	neutral	None	None	None	None	I
E/N	0.2869	likely_benign	0.3014	benign	-0.058	Destabilizing	0.809	D	0.592	neutral	None	None	None	None	I
E/P	0.7363	likely_pathogenic	0.739	pathogenic	0.081	Stabilizing	0.945	D	0.661	neutral	None	None	None	None	I
E/Q	0.121	likely_benign	0.1276	benign	-0.003	Destabilizing	0.864	D	0.587	neutral	N	0.512201482	None	None	I
E/R	0.2305	likely_benign	0.2547	benign	0.684	Stabilizing	0.945	D	0.631	neutral	None	None	None	None	I
E/S	0.2064	likely_benign	0.2143	benign	-0.184	Destabilizing	0.547	D	0.551	neutral	None	None	None	None	I
E/T	0.236	likely_benign	0.2393	benign	-0.014	Destabilizing	0.894	D	0.591	neutral	None	None	None	None	I
E/V	0.262	likely_benign	0.2721	benign	0.081	Stabilizing	0.928	D	0.649	neutral	N	0.485327616	None	None	I
E/W	0.8988	likely_pathogenic	0.9185	pathogenic	0.117	Stabilizing	0.995	D	0.715	prob.delet.	None	None	None	None	I
E/Y	0.6841	likely_pathogenic	0.7254	pathogenic	0.208	Stabilizing	0.981	D	0.669	neutral	None	None	None	None	I

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.