TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8275	25048;25049;25050	chr2:178718183;178718182;178718181	chr2:179582910;179582909;179582908
N2AB	7958	24097;24098;24099	chr2:178718183;178718182;178718181	chr2:179582910;179582909;179582908
N2A	7031	21316;21317;21318	chr2:178718183;178718182;178718181	chr2:179582910;179582909;179582908
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-68
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.2881
• 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
A/T	rs771947778	-1.281	0.01	N	0.149	0.216	0.300449992093	gnomAD-2.1.1	4.13E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.29E-05	None	0	0	0
A/T	rs771947778	-1.281	0.01	N	0.149	0.216	0.300449992093	gnomAD-4.0.0	1.10167E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.17018E-05	3.48554E-05	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
A/C	0.5739	likely_pathogenic	0.5324	ambiguous	-0.909	Destabilizing	0.966	D	0.541	neutral	None	None	None	None	I
A/D	0.5305	ambiguous	0.5873	pathogenic	-1.583	Destabilizing	0.758	D	0.599	neutral	None	None	None	None	I
A/E	0.4504	ambiguous	0.5197	ambiguous	-1.566	Destabilizing	0.99	D	0.531	neutral	N	0.491585494	None	None	I
A/F	0.5138	ambiguous	0.5454	ambiguous	-0.908	Destabilizing	0.981	D	0.606	neutral	None	None	None	None	I
A/G	0.1988	likely_benign	0.1972	benign	-1.328	Destabilizing	None	N	0.16	neutral	N	0.511358907	None	None	I
A/H	0.7113	likely_pathogenic	0.7457	pathogenic	-1.579	Destabilizing	0.998	D	0.563	neutral	None	None	None	None	I
A/I	0.2779	likely_benign	0.2649	benign	-0.294	Destabilizing	0.514	D	0.461	neutral	None	None	None	None	I
A/K	0.6467	likely_pathogenic	0.6873	pathogenic	-1.412	Destabilizing	0.997	D	0.53	neutral	None	None	None	None	I
A/L	0.2617	likely_benign	0.2782	benign	-0.294	Destabilizing	0.019	N	0.272	neutral	None	None	None	None	I
A/M	0.2619	likely_benign	0.2611	benign	-0.251	Destabilizing	0.981	D	0.591	neutral	None	None	None	None	I
A/N	0.4815	ambiguous	0.5012	ambiguous	-1.183	Destabilizing	0.269	N	0.617	neutral	None	None	None	None	I
A/P	0.7811	likely_pathogenic	0.8249	pathogenic	-0.493	Destabilizing	0.004	N	0.293	neutral	N	0.507968229	None	None	I
A/Q	0.5736	likely_pathogenic	0.6121	pathogenic	-1.279	Destabilizing	0.992	D	0.6	neutral	None	None	None	None	I
A/R	0.5825	likely_pathogenic	0.6376	pathogenic	-1.111	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	I
A/S	0.1432	likely_benign	0.1424	benign	-1.529	Destabilizing	0.018	N	0.413	neutral	N	0.485865817	None	None	I
A/T	0.0954	likely_benign	0.0888	benign	-1.421	Destabilizing	0.01	N	0.149	neutral	N	0.494599943	None	None	I
A/V	0.1042	likely_benign	0.0991	benign	-0.493	Destabilizing	0.002	N	0.124	neutral	N	0.397681111	None	None	I
A/W	0.8582	likely_pathogenic	0.8794	pathogenic	-1.371	Destabilizing	0.999	D	0.584	neutral	None	None	None	None	I
A/Y	0.6516	likely_pathogenic	0.6875	pathogenic	-0.949	Destabilizing	0.991	D	0.586	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.