TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5487	16684;16685;16686	chr2:178732602;178732601;178732600	chr2:179597329;179597328;179597327
N2AB	5170	15733;15734;15735	chr2:178732602;178732601;178732600	chr2:179597329;179597328;179597327
N2A	4243	12952;12953;12954	chr2:178732602;178732601;178732600	chr2:179597329;179597328;179597327
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-38
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.842
• 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	None	None	None	N	0.083	0.053	0.0482279557977	gnomAD-4.0.0	6.8426E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99496E-07	0	0
N/H	rs2080751190	None	0.065	N	0.247	0.062	0.0806252709748	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/H	rs2080751190	None	0.065	N	0.247	0.062	0.0806252709748	gnomAD-4.0.0	1.23951E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69528E-06	0	0
N/K	None	None	None	N	0.088	0.119	0.0762999501168	gnomAD-4.0.0	1.59156E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8586E-06	0	0
N/S	rs2080750786	None	0.003	N	0.196	0.07	0.0401082797425	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	1.30976E-04	0	0	0	None	0	0	0	0	0
N/S	rs2080750786	None	0.003	N	0.196	0.07	0.0401082797425	gnomAD-4.0.0	3.84387E-06	None	None	None	None	N	None	0	3.39087E-05	None	0	0	None	0	0	2.39329E-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	0.1327	likely_benign	0.1561	benign	-0.078	Destabilizing	0.002	N	0.227	neutral	None	None	None	None	N
N/C	0.2565	likely_benign	0.291	benign	0.025	Stabilizing	0.497	N	0.289	neutral	None	None	None	None	N
N/D	0.0575	likely_benign	0.0641	benign	0.156	Stabilizing	None	N	0.083	neutral	N	0.43748664	None	None	N
N/E	0.1179	likely_benign	0.1451	benign	0.094	Stabilizing	None	N	0.085	neutral	None	None	None	None	N
N/F	0.4104	ambiguous	0.488	ambiguous	-0.742	Destabilizing	0.022	N	0.395	neutral	None	None	None	None	N
N/G	0.1411	likely_benign	0.1704	benign	-0.148	Destabilizing	None	N	0.083	neutral	None	None	None	None	N
N/H	0.1111	likely_benign	0.1206	benign	-0.128	Destabilizing	0.065	N	0.247	neutral	N	0.500154039	None	None	N
N/I	0.1802	likely_benign	0.2087	benign	0.005	Stabilizing	0.007	N	0.291	neutral	N	0.453351937	None	None	N
N/K	0.1285	likely_benign	0.1534	benign	0.113	Stabilizing	None	N	0.088	neutral	N	0.463211804	None	None	N
N/L	0.1826	likely_benign	0.213	benign	0.005	Stabilizing	0.004	N	0.3	neutral	None	None	None	None	N
N/M	0.2508	likely_benign	0.2884	benign	-0.023	Destabilizing	0.245	N	0.275	neutral	None	None	None	None	N
N/P	0.2995	likely_benign	0.3387	benign	-0.001	Destabilizing	0.037	N	0.288	neutral	None	None	None	None	N
N/Q	0.1493	likely_benign	0.1763	benign	-0.281	Destabilizing	0.009	N	0.219	neutral	None	None	None	None	N
N/R	0.1595	likely_benign	0.1929	benign	0.184	Stabilizing	0.009	N	0.207	neutral	None	None	None	None	N
N/S	0.0703	likely_benign	0.0739	benign	-0.092	Destabilizing	0.003	N	0.196	neutral	N	0.394890656	None	None	N
N/T	0.1024	likely_benign	0.1146	benign	-0.045	Destabilizing	0.006	N	0.211	neutral	N	0.499460606	None	None	N
N/V	0.1638	likely_benign	0.1945	benign	-0.001	Destabilizing	None	N	0.171	neutral	None	None	None	None	N
N/W	0.5744	likely_pathogenic	0.6392	pathogenic	-0.908	Destabilizing	0.497	N	0.283	neutral	None	None	None	None	N
N/Y	0.1484	likely_benign	0.167	benign	-0.564	Destabilizing	None	N	0.15	neutral	N	0.461492239	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.