TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29633	89122;89123;89124	chr2:178554214;178554213;178554212	chr2:179418941;179418940;179418939
N2AB	27992	84199;84200;84201	chr2:178554214;178554213;178554212	chr2:179418941;179418940;179418939
N2A	27065	81418;81419;81420	chr2:178554214;178554213;178554212	chr2:179418941;179418940;179418939
N2B	20568	61927;61928;61929	chr2:178554214;178554213;178554212	chr2:179418941;179418940;179418939
Novex-1	20693	62302;62303;62304	chr2:178554214;178554213;178554212	chr2:179418941;179418940;179418939
Novex-2	20760	62503;62504;62505	chr2:178554214;178554213;178554212	chr2:179418941;179418940;179418939
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-104
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.6074
• 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
T/A	None	None	0.002	N	0.055	0.08	0.107399877778	gnomAD-4.0.0	1.67725E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.95919E-06	0	0
T/K	None	-0.109	0.651	N	0.485	0.28	0.34854441366	gnomAD-2.1.1	4.59E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.9E-06	0
T/K	None	-0.109	0.651	N	0.485	0.28	0.34854441366	gnomAD-4.0.0	1.67545E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.16877E-05

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
T/A	0.0873	likely_benign	0.0877	benign	-0.606	Destabilizing	0.002	N	0.055	neutral	N	0.403630357	None	None	I
T/C	0.3249	likely_benign	0.3388	benign	-0.261	Destabilizing	0.995	D	0.398	neutral	None	None	None	None	I
T/D	0.6277	likely_pathogenic	0.6279	pathogenic	-0.167	Destabilizing	0.834	D	0.575	neutral	None	None	None	None	I
T/E	0.4214	ambiguous	0.4052	ambiguous	-0.254	Destabilizing	0.712	D	0.524	neutral	None	None	None	None	I
T/F	0.3465	ambiguous	0.3643	ambiguous	-1.185	Destabilizing	0.946	D	0.523	neutral	None	None	None	None	I
T/G	0.4517	ambiguous	0.4839	ambiguous	-0.71	Destabilizing	0.338	N	0.415	neutral	None	None	None	None	I
T/H	0.3408	ambiguous	0.3514	ambiguous	-1.131	Destabilizing	0.018	N	0.345	neutral	None	None	None	None	I
T/I	0.1134	likely_benign	0.1108	benign	-0.444	Destabilizing	0.868	D	0.545	neutral	N	0.421506828	None	None	I
T/K	0.2664	likely_benign	0.2525	benign	-0.372	Destabilizing	0.651	D	0.485	neutral	N	0.396821815	None	None	I
T/L	0.0819	likely_benign	0.0791	benign	-0.444	Destabilizing	0.712	D	0.455	neutral	None	None	None	None	I
T/M	0.0806	likely_benign	0.0773	benign	0.052	Stabilizing	0.982	D	0.409	neutral	None	None	None	None	I
T/N	0.1919	likely_benign	0.1935	benign	-0.136	Destabilizing	0.712	D	0.379	neutral	None	None	None	None	I
T/P	0.0727	likely_benign	0.0716	benign	-0.473	Destabilizing	0.002	N	0.061	neutral	N	0.32357485	None	None	I
T/Q	0.256	likely_benign	0.2488	benign	-0.506	Destabilizing	0.946	D	0.547	neutral	None	None	None	None	I
T/R	0.2659	likely_benign	0.2549	benign	-0.051	Destabilizing	0.868	D	0.546	neutral	N	0.426259287	None	None	I
T/S	0.1615	likely_benign	0.1655	benign	-0.345	Destabilizing	0.278	N	0.367	neutral	N	0.46522032	None	None	I
T/V	0.0907	likely_benign	0.0882	benign	-0.473	Destabilizing	0.553	D	0.299	neutral	None	None	None	None	I
T/W	0.7646	likely_pathogenic	0.7709	pathogenic	-1.113	Destabilizing	0.995	D	0.536	neutral	None	None	None	None	I
T/Y	0.4016	ambiguous	0.3971	ambiguous	-0.846	Destabilizing	0.897	D	0.489	neutral	None	None	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.