TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8650	26173;26174;26175	chr2:178715238;178715237;178715236	chr2:179579965;179579964;179579963
N2AB	8333	25222;25223;25224	chr2:178715238;178715237;178715236	chr2:179579965;179579964;179579963
N2A	7406	22441;22442;22443	chr2:178715238;178715237;178715236	chr2:179579965;179579964;179579963
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: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-72
• Domain position: 8
• Structural Position: 9
• Q(SASA): 1.0215
• Predicted PPI site: I

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/N	None	None	0.001	N	0.254	0.084	0.0884992946249	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
H/Q	rs372385679	0.279	None	N	0.072	0.109	0.0482279557977	gnomAD-2.1.1	4.1E-06	None	None	None	None	I	None	6.5E-05	0	None	0	0	None	0	None	0	0	0
H/R	None	None	None	N	0.143	0.108	0.0551355673512	gnomAD-4.0.0	3.22006E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.76605E-06	0	0
H/Y	None	None	None	N	0.142	0.111	0.144782658237	gnomAD-4.0.0	7.20195E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.87503E-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	0.1141	likely_benign	0.1101	benign	0.584	Stabilizing	0.002	N	0.277	neutral	None	None	None	None	I
H/C	0.1055	likely_benign	0.1164	benign	0.745	Stabilizing	0.047	N	0.331	neutral	None	None	None	None	I
H/D	0.1136	likely_benign	0.1054	benign	-0.309	Destabilizing	None	N	0.105	neutral	N	0.456193484	None	None	I
H/E	0.1437	likely_benign	0.1388	benign	-0.301	Destabilizing	None	N	0.056	neutral	None	None	None	None	I
H/F	0.1503	likely_benign	0.1516	benign	1.115	Stabilizing	None	N	0.183	neutral	None	None	None	None	I
H/G	0.1513	likely_benign	0.1463	benign	0.363	Stabilizing	0.002	N	0.309	neutral	None	None	None	None	I
H/I	0.1251	likely_benign	0.1255	benign	1.128	Stabilizing	0.005	N	0.545	neutral	None	None	None	None	I
H/K	0.123	likely_benign	0.1226	benign	0.505	Stabilizing	0.001	N	0.273	neutral	None	None	None	None	I
H/L	0.0688	likely_benign	0.0675	benign	1.128	Stabilizing	0.001	N	0.357	neutral	N	0.44655528	None	None	I
H/M	0.2374	likely_benign	0.2336	benign	0.726	Stabilizing	0.061	N	0.362	neutral	None	None	None	None	I
H/N	0.0695	likely_benign	0.0688	benign	0.343	Stabilizing	0.001	N	0.254	neutral	N	0.45448133	None	None	I
H/P	0.0974	likely_benign	0.0931	benign	0.97	Stabilizing	None	N	0.149	neutral	N	0.452038458	None	None	I
H/Q	0.0874	likely_benign	0.0871	benign	0.404	Stabilizing	None	N	0.072	neutral	N	0.421387477	None	None	I
H/R	0.0732	likely_benign	0.0742	benign	-0.031	Destabilizing	None	N	0.143	neutral	N	0.405052588	None	None	I
H/S	0.0991	likely_benign	0.0953	benign	0.554	Stabilizing	None	N	0.111	neutral	None	None	None	None	I
H/T	0.1121	likely_benign	0.1105	benign	0.652	Stabilizing	None	N	0.135	neutral	None	None	None	None	I
H/V	0.1051	likely_benign	0.1056	benign	0.97	Stabilizing	0.002	N	0.35	neutral	None	None	None	None	I
H/W	0.2445	likely_benign	0.2553	benign	0.984	Stabilizing	0.197	N	0.323	neutral	None	None	None	None	I
H/Y	0.0652	likely_benign	0.065	benign	1.246	Stabilizing	None	N	0.142	neutral	N	0.474203242	None	None	I

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.