TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1574	4945;4946;4947	chr2:178777243;178777242;178777241	chr2:179641970;179641969;179641968
N2AB	1574	4945;4946;4947	chr2:178777243;178777242;178777241	chr2:179641970;179641969;179641968
N2A	1574	4945;4946;4947	chr2:178777243;178777242;178777241	chr2:179641970;179641969;179641968
N2B	1528	4807;4808;4809	chr2:178777243;178777242;178777241	chr2:179641970;179641969;179641968
Novex-1	1528	4807;4808;4809	chr2:178777243;178777242;178777241	chr2:179641970;179641969;179641968
Novex-2	1528	4807;4808;4809	chr2:178777243;178777242;178777241	chr2:179641970;179641969;179641968
Novex-3	1574	4945;4946;4947	chr2:178777243;178777242;178777241	chr2:179641970;179641969;179641968

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-7
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.4187
• 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/V	None	None	0.379	N	0.577	0.266	0.331619326243	gnomAD-4.0.0	1.59065E-06	None	None	None	None	N	None	0	0	None	4.76644E-05	0	None	0	0	0	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
E/A	0.1827	likely_benign	0.1608	benign	-0.692	Destabilizing	0.004	N	0.403	neutral	N	0.449265726	None	None	N
E/C	0.8838	likely_pathogenic	0.8533	pathogenic	-0.464	Destabilizing	0.977	D	0.63	neutral	None	None	None	None	N
E/D	0.1956	likely_benign	0.1837	benign	-0.875	Destabilizing	0.549	D	0.563	neutral	N	0.440913618	None	None	N
E/F	0.7473	likely_pathogenic	0.7076	pathogenic	-0.152	Destabilizing	0.92	D	0.619	neutral	None	None	None	None	N
E/G	0.3008	likely_benign	0.2674	benign	-1.011	Destabilizing	0.379	N	0.549	neutral	D	0.549274554	None	None	N
E/H	0.511	ambiguous	0.4479	ambiguous	-0.246	Destabilizing	0.026	N	0.443	neutral	None	None	None	None	N
E/I	0.3353	likely_benign	0.2944	benign	0.159	Stabilizing	0.85	D	0.622	neutral	None	None	None	None	N
E/K	0.2914	likely_benign	0.2528	benign	-0.433	Destabilizing	0.004	N	0.465	neutral	N	0.444521421	None	None	N
E/L	0.3999	ambiguous	0.3486	ambiguous	0.159	Stabilizing	0.447	N	0.572	neutral	None	None	None	None	N
E/M	0.4571	ambiguous	0.4093	ambiguous	0.36	Stabilizing	0.977	D	0.597	neutral	None	None	None	None	N
E/N	0.3328	likely_benign	0.2953	benign	-0.863	Destabilizing	0.617	D	0.525	neutral	None	None	None	None	N
E/P	0.9548	likely_pathogenic	0.9355	pathogenic	-0.104	Destabilizing	0.92	D	0.563	neutral	None	None	None	None	N
E/Q	0.16	likely_benign	0.1419	benign	-0.762	Destabilizing	0.016	N	0.328	neutral	N	0.450321553	None	None	N
E/R	0.4143	ambiguous	0.3667	ambiguous	-0.083	Destabilizing	0.447	N	0.51	neutral	None	None	None	None	N
E/S	0.2299	likely_benign	0.2055	benign	-1.108	Destabilizing	0.447	N	0.545	neutral	None	None	None	None	N
E/T	0.2262	likely_benign	0.1967	benign	-0.852	Destabilizing	0.617	D	0.505	neutral	None	None	None	None	N
E/V	0.2041	likely_benign	0.1789	benign	-0.104	Destabilizing	0.379	N	0.577	neutral	N	0.43965954	None	None	N
E/W	0.9146	likely_pathogenic	0.8928	pathogenic	0.101	Stabilizing	0.992	D	0.666	neutral	None	None	None	None	N
E/Y	0.677	likely_pathogenic	0.6356	pathogenic	0.092	Stabilizing	0.85	D	0.606	neutral	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.