TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3857	11794;11795;11796	chr2:178741664;178741663;178741662	chr2:179606391;179606390;179606389
N2AB	3540	10843;10844;10845	chr2:178741664;178741663;178741662	chr2:179606391;179606390;179606389
N2A	None	None	chr2:None	chr2:None
N2B	3494	10705;10706;10707	chr2:178741664;178741663;178741662	chr2:179606391;179606390;179606389
Novex-1	3619	11080;11081;11082	chr2:178741664;178741663;178741662	chr2:179606391;179606390;179606389
Novex-2	3686	11281;11282;11283	chr2:178741664;178741663;178741662	chr2:179606391;179606390;179606389
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-27
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.4249
• 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
G/R	rs777025488	-0.353	0.982	D	0.583	0.439	None	gnomAD-4.0.0	1.27299E-05	None	None	None	None	I	None	0	0	None	0	0	None	1.12952E-04	0	5.71651E-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
G/A	0.3789	ambiguous	0.3568	ambiguous	-0.354	Destabilizing	0.885	D	0.378	neutral	D	0.562608104	None	None	I
G/C	0.5253	ambiguous	0.4815	ambiguous	-0.906	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	I
G/D	0.1704	likely_benign	0.1879	benign	-0.386	Destabilizing	0.91	D	0.501	neutral	None	None	None	None	I
G/E	0.2799	likely_benign	0.2745	benign	-0.518	Destabilizing	0.1	N	0.329	neutral	N	0.467559123	None	None	I
G/F	0.9154	likely_pathogenic	0.9065	pathogenic	-0.896	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	I
G/H	0.4853	ambiguous	0.4861	ambiguous	-0.524	Destabilizing	0.998	D	0.585	neutral	None	None	None	None	I
G/I	0.8532	likely_pathogenic	0.8213	pathogenic	-0.383	Destabilizing	0.993	D	0.684	prob.neutral	None	None	None	None	I
G/K	0.4587	ambiguous	0.4363	ambiguous	-0.853	Destabilizing	0.973	D	0.533	neutral	None	None	None	None	I
G/L	0.874	likely_pathogenic	0.8568	pathogenic	-0.383	Destabilizing	0.986	D	0.671	neutral	None	None	None	None	I
G/M	0.8569	likely_pathogenic	0.8295	pathogenic	-0.538	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	I
G/N	0.2746	likely_benign	0.2977	benign	-0.573	Destabilizing	0.128	N	0.318	neutral	None	None	None	None	I
G/P	0.9902	likely_pathogenic	0.99	pathogenic	-0.338	Destabilizing	0.993	D	0.581	neutral	None	None	None	None	I
G/Q	0.4132	ambiguous	0.4116	ambiguous	-0.793	Destabilizing	0.986	D	0.579	neutral	None	None	None	None	I
G/R	0.321	likely_benign	0.2941	benign	-0.435	Destabilizing	0.982	D	0.583	neutral	D	0.599530278	None	None	I
G/S	0.1353	likely_benign	0.1405	benign	-0.774	Destabilizing	0.386	N	0.283	neutral	None	None	None	None	I
G/T	0.4722	ambiguous	0.4621	ambiguous	-0.823	Destabilizing	0.973	D	0.533	neutral	None	None	None	None	I
G/V	0.7531	likely_pathogenic	0.7175	pathogenic	-0.338	Destabilizing	0.982	D	0.665	neutral	D	0.717100599	None	None	I
G/W	0.786	likely_pathogenic	0.7651	pathogenic	-1.083	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	I
G/Y	0.742	likely_pathogenic	0.7319	pathogenic	-0.727	Destabilizing	0.999	D	0.673	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.