TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27995	84208;84209;84210	chr2:178562149;178562148;178562147	chr2:179426876;179426875;179426874
N2AB	26354	79285;79286;79287	chr2:178562149;178562148;178562147	chr2:179426876;179426875;179426874
N2A	25427	76504;76505;76506	chr2:178562149;178562148;178562147	chr2:179426876;179426875;179426874
N2B	18930	57013;57014;57015	chr2:178562149;178562148;178562147	chr2:179426876;179426875;179426874
Novex-1	19055	57388;57389;57390	chr2:178562149;178562148;178562147	chr2:179426876;179426875;179426874
Novex-2	19122	57589;57590;57591	chr2:178562149;178562148;178562147	chr2:179426876;179426875;179426874
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-142
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.5834
• 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
N/T	rs751728774	-0.027	None	N	0.115	0.084	0.0482279557977	gnomAD-2.1.1	8.1E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
N/T	rs751728774	-0.027	None	N	0.115	0.084	0.0482279557977	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/T	rs751728774	-0.027	None	N	0.115	0.084	0.0482279557977	gnomAD-4.0.0	4.95929E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.78203E-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
N/A	0.0914	likely_benign	0.0834	benign	-0.783	Destabilizing	None	N	0.267	neutral	None	None	None	None	N
N/C	0.112	likely_benign	0.1048	benign	0.128	Stabilizing	0.245	N	0.489	neutral	None	None	None	None	N
N/D	0.1056	likely_benign	0.113	benign	-0.404	Destabilizing	0.003	N	0.298	neutral	N	0.478358268	None	None	N
N/E	0.1773	likely_benign	0.174	benign	-0.339	Destabilizing	0.004	N	0.293	neutral	None	None	None	None	N
N/F	0.1943	likely_benign	0.1698	benign	-0.64	Destabilizing	0.044	N	0.523	neutral	None	None	None	None	N
N/G	0.1664	likely_benign	0.1639	benign	-1.099	Destabilizing	0.002	N	0.299	neutral	None	None	None	None	N
N/H	0.0691	likely_benign	0.0691	benign	-0.949	Destabilizing	0.196	N	0.41	neutral	N	0.423198418	None	None	N
N/I	0.0724	likely_benign	0.0639	benign	0.008	Stabilizing	None	N	0.374	neutral	N	0.410269193	None	None	N
N/K	0.1526	likely_benign	0.1512	benign	-0.26	Destabilizing	0.003	N	0.289	neutral	N	0.402879074	None	None	N
N/L	0.0877	likely_benign	0.0782	benign	0.008	Stabilizing	0.001	N	0.371	neutral	None	None	None	None	N
N/M	0.1376	likely_benign	0.1209	benign	0.473	Stabilizing	0.138	N	0.519	neutral	None	None	None	None	N
N/P	0.7634	likely_pathogenic	0.8059	pathogenic	-0.226	Destabilizing	0.018	N	0.431	neutral	None	None	None	None	N
N/Q	0.1514	likely_benign	0.1428	benign	-0.784	Destabilizing	0.001	N	0.162	neutral	None	None	None	None	N
N/R	0.1625	likely_benign	0.158	benign	-0.286	Destabilizing	0.018	N	0.335	neutral	None	None	None	None	N
N/S	0.0514	likely_benign	0.0494	benign	-0.737	Destabilizing	None	N	0.114	neutral	N	0.322625992	None	None	N
N/T	0.0486	likely_benign	0.0458	benign	-0.487	Destabilizing	None	N	0.115	neutral	N	0.317241602	None	None	N
N/V	0.0809	likely_benign	0.0722	benign	-0.226	Destabilizing	0.001	N	0.373	neutral	None	None	None	None	N
N/W	0.4593	ambiguous	0.4521	ambiguous	-0.435	Destabilizing	0.788	D	0.484	neutral	None	None	None	None	N
N/Y	0.0917	likely_benign	0.0908	benign	-0.24	Destabilizing	0.065	N	0.503	neutral	N	0.449768944	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.