TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31924	95995;95996;95997	chr2:178544459;178544458;178544457	chr2:179409186;179409185;179409184
N2AB	30283	91072;91073;91074	chr2:178544459;178544458;178544457	chr2:179409186;179409185;179409184
N2A	29356	88291;88292;88293	chr2:178544459;178544458;178544457	chr2:179409186;179409185;179409184
N2B	22859	68800;68801;68802	chr2:178544459;178544458;178544457	chr2:179409186;179409185;179409184
Novex-1	22984	69175;69176;69177	chr2:178544459;178544458;178544457	chr2:179409186;179409185;179409184
Novex-2	23051	69376;69377;69378	chr2:178544459;178544458;178544457	chr2:179409186;179409185;179409184
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-121
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.3536
• 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
H/Q	rs747894883	-0.385	0.055	N	0.189	0.096	0.277317399466	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
H/Q	rs747894883	-0.385	0.055	N	0.189	0.096	0.277317399466	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
H/Q	rs747894883	-0.385	0.055	N	0.189	0.096	0.277317399466	gnomAD-4.0.0	3.85105E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.20298E-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
H/A	0.2004	likely_benign	0.1639	benign	0.016	Stabilizing	0.007	N	0.249	neutral	None	None	None	None	N
H/C	0.1335	likely_benign	0.1222	benign	0.618	Stabilizing	0.628	D	0.303	neutral	None	None	None	None	N
H/D	0.1404	likely_benign	0.1239	benign	0.15	Stabilizing	0.055	N	0.279	neutral	N	0.411311264	None	None	N
H/E	0.2041	likely_benign	0.1764	benign	0.178	Stabilizing	0.016	N	0.187	neutral	None	None	None	None	N
H/F	0.2406	likely_benign	0.1895	benign	0.573	Stabilizing	None	N	0.211	neutral	None	None	None	None	N
H/G	0.1787	likely_benign	0.1653	benign	-0.279	Destabilizing	0.016	N	0.245	neutral	None	None	None	None	N
H/I	0.3316	likely_benign	0.2687	benign	0.774	Stabilizing	0.038	N	0.412	neutral	None	None	None	None	N
H/K	0.1497	likely_benign	0.1316	benign	0.051	Stabilizing	None	N	0.147	neutral	None	None	None	None	N
H/L	0.1277	likely_benign	0.1118	benign	0.774	Stabilizing	0.012	N	0.273	neutral	N	0.474976409	None	None	N
H/M	0.3345	likely_benign	0.2912	benign	0.663	Stabilizing	0.356	N	0.307	neutral	None	None	None	None	N
H/N	0.0691	likely_benign	0.0664	benign	0.214	Stabilizing	0.024	N	0.15	neutral	N	0.392570788	None	None	N
H/P	0.5518	ambiguous	0.5014	ambiguous	0.547	Stabilizing	0.106	N	0.404	neutral	N	0.492121707	None	None	N
H/Q	0.1088	likely_benign	0.1025	benign	0.306	Stabilizing	0.055	N	0.189	neutral	N	0.475440101	None	None	N
H/R	0.0799	likely_benign	0.0732	benign	-0.451	Destabilizing	None	N	0.055	neutral	N	0.43434284	None	None	N
H/S	0.1253	likely_benign	0.1095	benign	0.192	Stabilizing	None	N	0.145	neutral	None	None	None	None	N
H/T	0.1261	likely_benign	0.1064	benign	0.318	Stabilizing	None	N	0.158	neutral	None	None	None	None	N
H/V	0.2598	likely_benign	0.2104	benign	0.547	Stabilizing	0.016	N	0.269	neutral	None	None	None	None	N
H/W	0.3203	likely_benign	0.2786	benign	0.612	Stabilizing	0.356	N	0.293	neutral	None	None	None	None	N
H/Y	0.0946	likely_benign	0.0765	benign	0.938	Stabilizing	None	N	0.1	neutral	N	0.470861	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.