TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25467	76624;76625;76626	chr2:178569733;178569732;178569731	chr2:179434460;179434459;179434458
N2AB	23826	71701;71702;71703	chr2:178569733;178569732;178569731	chr2:179434460;179434459;179434458
N2A	22899	68920;68921;68922	chr2:178569733;178569732;178569731	chr2:179434460;179434459;179434458
N2B	16402	49429;49430;49431	chr2:178569733;178569732;178569731	chr2:179434460;179434459;179434458
Novex-1	16527	49804;49805;49806	chr2:178569733;178569732;178569731	chr2:179434460;179434459;179434458
Novex-2	16594	50005;50006;50007	chr2:178569733;178569732;178569731	chr2:179434460;179434459;179434458
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-73
• Domain position: 63
• Structural Position: 92
• Q(SASA): 0.2905
• 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
E/K	rs758729188	-0.084	0.014	N	0.347	0.175	0.21737058555	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
E/K	rs758729188	-0.084	0.014	N	0.347	0.175	0.21737058555	gnomAD-4.0.0	1.27406E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.00333E-04	3.02755E-05

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
E/A	0.1308	likely_benign	0.1196	benign	-0.976	Destabilizing	0.698	D	0.575	neutral	N	0.452333954	None	None	N
E/C	0.7152	likely_pathogenic	0.688	pathogenic	-0.427	Destabilizing	0.998	D	0.748	deleterious	None	None	None	None	N
E/D	0.3013	likely_benign	0.259	benign	-0.665	Destabilizing	0.822	D	0.501	neutral	N	0.466167256	None	None	N
E/F	0.7425	likely_pathogenic	0.6812	pathogenic	-0.35	Destabilizing	0.993	D	0.761	deleterious	None	None	None	None	N
E/G	0.2824	likely_benign	0.2439	benign	-1.279	Destabilizing	0.822	D	0.647	neutral	N	0.489564191	None	None	N
E/H	0.4529	ambiguous	0.3937	ambiguous	-0.268	Destabilizing	0.994	D	0.579	neutral	None	None	None	None	N
E/I	0.2486	likely_benign	0.2196	benign	-0.16	Destabilizing	0.956	D	0.754	deleterious	None	None	None	None	N
E/K	0.1194	likely_benign	0.1008	benign	-0.132	Destabilizing	0.014	N	0.347	neutral	N	0.445175909	None	None	N
E/L	0.3136	likely_benign	0.2664	benign	-0.16	Destabilizing	0.86	D	0.662	neutral	None	None	None	None	N
E/M	0.3359	likely_benign	0.2905	benign	0.149	Stabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
E/N	0.3536	ambiguous	0.311	benign	-0.777	Destabilizing	0.956	D	0.549	neutral	None	None	None	None	N
E/P	0.5268	ambiguous	0.4782	ambiguous	-0.413	Destabilizing	0.978	D	0.691	prob.neutral	None	None	None	None	N
E/Q	0.1238	likely_benign	0.1149	benign	-0.671	Destabilizing	0.942	D	0.534	neutral	N	0.456296979	None	None	N
E/R	0.2321	likely_benign	0.1942	benign	0.211	Stabilizing	0.754	D	0.523	neutral	None	None	None	None	N
E/S	0.2494	likely_benign	0.224	benign	-0.991	Destabilizing	0.754	D	0.495	neutral	None	None	None	None	N
E/T	0.1728	likely_benign	0.1581	benign	-0.723	Destabilizing	0.076	N	0.331	neutral	None	None	None	None	N
E/V	0.1484	likely_benign	0.1353	benign	-0.413	Destabilizing	0.822	D	0.653	neutral	N	0.437633861	None	None	N
E/W	0.9233	likely_pathogenic	0.8846	pathogenic	0.03	Stabilizing	0.998	D	0.728	prob.delet.	None	None	None	None	N
E/Y	0.6529	likely_pathogenic	0.5837	pathogenic	-0.056	Destabilizing	0.993	D	0.755	deleterious	None	None	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.