TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6528	19807;19808;19809	chr2:178728242;178728241;178728240	chr2:179592969;179592968;179592967
N2AB	6211	18856;18857;18858	chr2:178728242;178728241;178728240	chr2:179592969;179592968;179592967
N2A	5284	16075;16076;16077	chr2:178728242;178728241;178728240	chr2:179592969;179592968;179592967
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-49
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.5627
• 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
R/K	rs779960008	-0.334	0.001	N	0.151	0.099	0.208000267992	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
R/K	rs779960008	-0.334	0.001	N	0.151	0.099	0.208000267992	gnomAD-4.0.0	1.59265E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43345E-05	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
R/A	0.2876	likely_benign	0.3365	benign	-0.421	Destabilizing	0.25	N	0.443	neutral	None	None	None	None	N
R/C	0.145	likely_benign	0.1769	benign	-0.425	Destabilizing	0.992	D	0.545	neutral	None	None	None	None	N
R/D	0.4503	ambiguous	0.527	ambiguous	0.013	Stabilizing	0.617	D	0.514	neutral	None	None	None	None	N
R/E	0.2579	likely_benign	0.306	benign	0.095	Stabilizing	0.25	N	0.418	neutral	None	None	None	None	N
R/F	0.3923	ambiguous	0.4478	ambiguous	-0.524	Destabilizing	0.972	D	0.537	neutral	None	None	None	None	N
R/G	0.1883	likely_benign	0.2263	benign	-0.665	Destabilizing	0.549	D	0.481	neutral	N	0.488392263	None	None	N
R/H	0.0699	likely_benign	0.0746	benign	-1.031	Destabilizing	0.92	D	0.462	neutral	None	None	None	None	N
R/I	0.1678	likely_benign	0.1806	benign	0.205	Stabilizing	0.896	D	0.531	neutral	N	0.502968711	None	None	N
R/K	0.0982	likely_benign	0.1044	benign	-0.399	Destabilizing	0.001	N	0.151	neutral	N	0.431604471	None	None	N
R/L	0.1682	likely_benign	0.19	benign	0.205	Stabilizing	0.617	D	0.481	neutral	None	None	None	None	N
R/M	0.2095	likely_benign	0.2325	benign	-0.093	Destabilizing	0.972	D	0.505	neutral	None	None	None	None	N
R/N	0.3359	likely_benign	0.3856	ambiguous	0.061	Stabilizing	0.617	D	0.439	neutral	None	None	None	None	N
R/P	0.7495	likely_pathogenic	0.7906	pathogenic	0.017	Stabilizing	0.92	D	0.503	neutral	None	None	None	None	N
R/Q	0.0811	likely_benign	0.0874	benign	-0.149	Destabilizing	0.447	N	0.472	neutral	None	None	None	None	N
R/S	0.2593	likely_benign	0.3074	benign	-0.567	Destabilizing	0.379	N	0.455	neutral	N	0.496752027	None	None	N
R/T	0.1437	likely_benign	0.1567	benign	-0.329	Destabilizing	0.549	D	0.481	neutral	N	0.47597411	None	None	N
R/V	0.2364	likely_benign	0.2682	benign	0.017	Stabilizing	0.85	D	0.497	neutral	None	None	None	None	N
R/W	0.1491	likely_benign	0.1634	benign	-0.351	Destabilizing	0.992	D	0.591	neutral	None	None	None	None	N
R/Y	0.2732	likely_benign	0.3247	benign	0.01	Stabilizing	0.972	D	0.543	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.