TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9045	27358;27359;27360	chr2:178712892;178712891;178712890	chr2:179577619;179577618;179577617
N2AB	8728	26407;26408;26409	chr2:178712892;178712891;178712890	chr2:179577619;179577618;179577617
N2A	7801	23626;23627;23628	chr2:178712892;178712891;178712890	chr2:179577619;179577618;179577617
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-76
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.57
• 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
T/A	None	None	0.001	N	0.183	0.085	0.229924730088	gnomAD-4.0.0	1.59199E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85896E-06	0	0
T/K	None	None	0.062	N	0.392	0.212	0.37568098594	gnomAD-4.0.0	6.8436E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99552E-07	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
T/A	0.1268	likely_benign	0.1509	benign	-0.372	Destabilizing	0.001	N	0.183	neutral	N	0.519012811	None	None	I
T/C	0.5901	likely_pathogenic	0.6996	pathogenic	-0.399	Destabilizing	0.824	D	0.457	neutral	None	None	None	None	I
T/D	0.4392	ambiguous	0.4713	ambiguous	0.095	Stabilizing	0.081	N	0.453	neutral	None	None	None	None	I
T/E	0.3945	ambiguous	0.454	ambiguous	0.056	Stabilizing	0.081	N	0.39	neutral	None	None	None	None	I
T/F	0.2442	likely_benign	0.3128	benign	-0.749	Destabilizing	0.555	D	0.581	neutral	None	None	None	None	I
T/G	0.3766	ambiguous	0.4398	ambiguous	-0.538	Destabilizing	0.035	N	0.517	neutral	None	None	None	None	I
T/H	0.2931	likely_benign	0.3293	benign	-0.659	Destabilizing	0.824	D	0.571	neutral	None	None	None	None	I
T/I	0.2599	likely_benign	0.325	benign	-0.044	Destabilizing	0.317	N	0.436	neutral	N	0.484188754	None	None	I
T/K	0.275	likely_benign	0.3295	benign	-0.432	Destabilizing	0.062	N	0.392	neutral	N	0.485768462	None	None	I
T/L	0.1515	likely_benign	0.1757	benign	-0.044	Destabilizing	0.149	N	0.386	neutral	None	None	None	None	I
T/M	0.1052	likely_benign	0.1188	benign	-0.171	Destabilizing	0.791	D	0.459	neutral	None	None	None	None	I
T/N	0.1477	likely_benign	0.1631	benign	-0.296	Destabilizing	0.081	N	0.395	neutral	None	None	None	None	I
T/P	0.339	likely_benign	0.4038	ambiguous	-0.124	Destabilizing	0.317	N	0.446	neutral	N	0.513902804	None	None	I
T/Q	0.2809	likely_benign	0.3289	benign	-0.429	Destabilizing	0.38	N	0.467	neutral	None	None	None	None	I
T/R	0.2257	likely_benign	0.2754	benign	-0.145	Destabilizing	0.317	N	0.446	neutral	D	0.526170857	None	None	I
T/S	0.0956	likely_benign	0.0996	benign	-0.496	Destabilizing	None	N	0.189	neutral	N	0.436685003	None	None	I
T/V	0.213	likely_benign	0.2643	benign	-0.124	Destabilizing	0.149	N	0.329	neutral	None	None	None	None	I
T/W	0.5827	likely_pathogenic	0.6692	pathogenic	-0.805	Destabilizing	0.935	D	0.634	neutral	None	None	None	None	I
T/Y	0.288	likely_benign	0.354	ambiguous	-0.508	Destabilizing	0.555	D	0.589	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.