TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23154	69685;69686;69687	chr2:178576784;178576783;178576782	chr2:179441511;179441510;179441509
N2AB	21513	64762;64763;64764	chr2:178576784;178576783;178576782	chr2:179441511;179441510;179441509
N2A	20586	61981;61982;61983	chr2:178576784;178576783;178576782	chr2:179441511;179441510;179441509
N2B	14089	42490;42491;42492	chr2:178576784;178576783;178576782	chr2:179441511;179441510;179441509
Novex-1	14214	42865;42866;42867	chr2:178576784;178576783;178576782	chr2:179441511;179441510;179441509
Novex-2	14281	43066;43067;43068	chr2:178576784;178576783;178576782	chr2:179441511;179441510;179441509
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: Fn3-56
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.3351
• 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/D	rs1486007034	None	0.004	N	0.21	0.102	0.19670166235	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/D	rs1486007034	None	0.004	N	0.21	0.102	0.19670166235	gnomAD-4.0.0	2.03012E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.40995E-06	0	0
N/I	None	None	0.81	N	0.471	0.218	0.457106177737	gnomAD-4.0.0	1.592E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85945E-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	0.2683	likely_benign	0.245	benign	-0.651	Destabilizing	0.25	N	0.37	neutral	None	None	None	None	N
N/C	0.3472	ambiguous	0.3196	benign	0.067	Stabilizing	0.992	D	0.474	neutral	None	None	None	None	N
N/D	0.1436	likely_benign	0.1439	benign	-1.075	Destabilizing	0.004	N	0.21	neutral	N	0.406908309	None	None	N
N/E	0.3547	ambiguous	0.35	ambiguous	-1.047	Destabilizing	0.447	N	0.342	neutral	None	None	None	None	N
N/F	0.5082	ambiguous	0.4704	ambiguous	-0.789	Destabilizing	0.92	D	0.469	neutral	None	None	None	None	N
N/G	0.3158	likely_benign	0.292	benign	-0.906	Destabilizing	0.25	N	0.367	neutral	None	None	None	None	N
N/H	0.1401	likely_benign	0.1331	benign	-0.849	Destabilizing	0.896	D	0.415	neutral	N	0.491239059	None	None	N
N/I	0.3246	likely_benign	0.3279	benign	-0.038	Destabilizing	0.81	D	0.471	neutral	N	0.477942604	None	None	N
N/K	0.3649	ambiguous	0.3618	ambiguous	-0.179	Destabilizing	0.379	N	0.367	neutral	N	0.518732305	None	None	N
N/L	0.3107	likely_benign	0.2935	benign	-0.038	Destabilizing	0.447	N	0.433	neutral	None	None	None	None	N
N/M	0.305	likely_benign	0.2852	benign	0.631	Stabilizing	0.992	D	0.417	neutral	None	None	None	None	N
N/P	0.9417	likely_pathogenic	0.9425	pathogenic	-0.215	Destabilizing	0.92	D	0.444	neutral	None	None	None	None	N
N/Q	0.3248	likely_benign	0.3137	benign	-1.008	Destabilizing	0.85	D	0.427	neutral	None	None	None	None	N
N/R	0.4502	ambiguous	0.4421	ambiguous	0.004	Stabilizing	0.85	D	0.409	neutral	None	None	None	None	N
N/S	0.1061	likely_benign	0.1024	benign	-0.666	Destabilizing	0.007	N	0.091	neutral	N	0.445194551	None	None	N
N/T	0.1187	likely_benign	0.1045	benign	-0.483	Destabilizing	0.016	N	0.202	neutral	N	0.452579097	None	None	N
N/V	0.3115	likely_benign	0.3002	benign	-0.215	Destabilizing	0.739	D	0.437	neutral	None	None	None	None	N
N/W	0.7746	likely_pathogenic	0.765	pathogenic	-0.622	Destabilizing	0.992	D	0.575	neutral	None	None	None	None	N
N/Y	0.1575	likely_benign	0.1556	benign	-0.36	Destabilizing	0.963	D	0.435	neutral	N	0.484690554	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.