TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6588	19987;19988;19989	chr2:178727816;178727815;178727814	chr2:179592543;179592542;179592541
N2AB	6271	19036;19037;19038	chr2:178727816;178727815;178727814	chr2:179592543;179592542;179592541
N2A	5344	16255;16256;16257	chr2:178727816;178727815;178727814	chr2:179592543;179592542;179592541
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-50
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.746
• 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
D/H	None	None	0.988	N	0.593	0.398	0.39843156188	gnomAD-4.0.0	6.85357E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00526E-06	0	0
D/N	None	None	0.061	N	0.301	0.224	0.233785782151	gnomAD-4.0.0	6.85357E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00526E-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
D/A	0.1764	likely_benign	0.147	benign	-0.172	Destabilizing	0.92	D	0.531	neutral	N	0.494463871	None	None	N
D/C	0.7033	likely_pathogenic	0.651	pathogenic	0.182	Stabilizing	0.999	D	0.634	neutral	None	None	None	None	N
D/E	0.1997	likely_benign	0.1759	benign	-0.178	Destabilizing	0.92	D	0.421	neutral	N	0.476550113	None	None	N
D/F	0.5842	likely_pathogenic	0.5453	ambiguous	-0.265	Destabilizing	0.997	D	0.615	neutral	None	None	None	None	N
D/G	0.1084	likely_benign	0.0933	benign	-0.321	Destabilizing	0.015	N	0.399	neutral	N	0.310005333	None	None	N
D/H	0.3015	likely_benign	0.2494	benign	-0.035	Destabilizing	0.988	D	0.593	neutral	N	0.489949198	None	None	N
D/I	0.5203	ambiguous	0.4383	ambiguous	0.159	Stabilizing	0.997	D	0.606	neutral	None	None	None	None	N
D/K	0.4345	ambiguous	0.3496	ambiguous	0.509	Stabilizing	0.939	D	0.565	neutral	None	None	None	None	N
D/L	0.4384	ambiguous	0.371	ambiguous	0.159	Stabilizing	0.991	D	0.6	neutral	None	None	None	None	N
D/M	0.6894	likely_pathogenic	0.6381	pathogenic	0.284	Stabilizing	0.999	D	0.617	neutral	None	None	None	None	N
D/N	0.0958	likely_benign	0.0802	benign	0.294	Stabilizing	0.061	N	0.301	neutral	N	0.437378437	None	None	N
D/P	0.7825	likely_pathogenic	0.7431	pathogenic	0.069	Stabilizing	0.997	D	0.573	neutral	None	None	None	None	N
D/Q	0.383	ambiguous	0.3209	benign	0.303	Stabilizing	0.991	D	0.439	neutral	None	None	None	None	N
D/R	0.4226	ambiguous	0.3569	ambiguous	0.586	Stabilizing	0.991	D	0.579	neutral	None	None	None	None	N
D/S	0.1289	likely_benign	0.111	benign	0.196	Stabilizing	0.863	D	0.395	neutral	None	None	None	None	N
D/T	0.3192	likely_benign	0.2661	benign	0.313	Stabilizing	0.939	D	0.569	neutral	None	None	None	None	N
D/V	0.3233	likely_benign	0.2665	benign	0.069	Stabilizing	0.996	D	0.605	neutral	N	0.489949198	None	None	N
D/W	0.8931	likely_pathogenic	0.8833	pathogenic	-0.189	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
D/Y	0.2416	likely_benign	0.2211	benign	-0.037	Destabilizing	0.996	D	0.617	neutral	N	0.490202688	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.