TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35471	106636;106637;106638	chr2:178530080;178530079;178530078	chr2:179394807;179394806;179394805
N2AB	33830	101713;101714;101715	chr2:178530080;178530079;178530078	chr2:179394807;179394806;179394805
N2A	32903	98932;98933;98934	chr2:178530080;178530079;178530078	chr2:179394807;179394806;179394805
N2B	26406	79441;79442;79443	chr2:178530080;178530079;178530078	chr2:179394807;179394806;179394805
Novex-1	26531	79816;79817;79818	chr2:178530080;178530079;178530078	chr2:179394807;179394806;179394805
Novex-2	26598	80017;80018;80019	chr2:178530080;178530079;178530078	chr2:179394807;179394806;179394805
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-166
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.5364
• 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/N	None	None	None	N	0.097	0.127	0.241078983079	gnomAD-4.0.0	6.86113E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00263E-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	0.1912	likely_benign	0.1675	benign	-0.245	Destabilizing	None	N	0.124	neutral	N	0.512529556	None	None	N
D/C	0.7189	likely_pathogenic	0.6791	pathogenic	-0.045	Destabilizing	0.448	N	0.342	neutral	None	None	None	None	N
D/E	0.1473	likely_benign	0.122	benign	-0.225	Destabilizing	None	N	0.068	neutral	N	0.426852012	None	None	N
D/F	0.5394	ambiguous	0.4924	ambiguous	-0.154	Destabilizing	0.177	N	0.377	neutral	None	None	None	None	N
D/G	0.1493	likely_benign	0.1275	benign	-0.405	Destabilizing	None	N	0.108	neutral	N	0.515012501	None	None	N
D/H	0.3203	likely_benign	0.2878	benign	0.189	Stabilizing	0.074	N	0.276	neutral	D	0.522997266	None	None	N
D/I	0.3098	likely_benign	0.2915	benign	0.122	Stabilizing	0.096	N	0.45	neutral	None	None	None	None	N
D/K	0.3095	likely_benign	0.2998	benign	0.468	Stabilizing	None	N	0.133	neutral	None	None	None	None	N
D/L	0.3844	ambiguous	0.358	ambiguous	0.122	Stabilizing	0.015	N	0.343	neutral	None	None	None	None	N
D/M	0.5897	likely_pathogenic	0.545	ambiguous	0.137	Stabilizing	0.396	N	0.337	neutral	None	None	None	None	N
D/N	0.1132	likely_benign	0.0988	benign	0.073	Stabilizing	None	N	0.097	neutral	N	0.457060276	None	None	N
D/P	0.7856	likely_pathogenic	0.7435	pathogenic	0.02	Stabilizing	0.058	N	0.349	neutral	None	None	None	None	N
D/Q	0.3177	likely_benign	0.2884	benign	0.111	Stabilizing	0.015	N	0.142	neutral	None	None	None	None	N
D/R	0.3714	ambiguous	0.3564	ambiguous	0.633	Stabilizing	0.015	N	0.324	neutral	None	None	None	None	N
D/S	0.1473	likely_benign	0.129	benign	0.008	Stabilizing	0.006	N	0.211	neutral	None	None	None	None	N
D/T	0.248	likely_benign	0.2272	benign	0.146	Stabilizing	0.006	N	0.266	neutral	None	None	None	None	N
D/V	0.1968	likely_benign	0.1838	benign	0.02	Stabilizing	0.011	N	0.349	neutral	N	0.514319068	None	None	N
D/W	0.8303	likely_pathogenic	0.8171	pathogenic	-0.013	Destabilizing	0.712	D	0.366	neutral	None	None	None	None	N
D/Y	0.213	likely_benign	0.1991	benign	0.089	Stabilizing	0.331	N	0.376	neutral	N	0.505104166	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.