TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7586	22981;22982;22983	chr2:178721907;178721906;178721905	chr2:179586634;179586633;179586632
N2AB	7269	22030;22031;22032	chr2:178721907;178721906;178721905	chr2:179586634;179586633;179586632
N2A	6342	19249;19250;19251	chr2:178721907;178721906;178721905	chr2:179586634;179586633;179586632
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-60
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1603
• 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
T/I	None	None	0.994	N	0.755	0.276	0.501685917333	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
T/A	0.1065	likely_benign	0.1046	benign	-0.736	Destabilizing	0.415	N	0.679	prob.neutral	N	0.473497335	None	None	N
T/C	0.4855	ambiguous	0.4734	ambiguous	-0.934	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
T/D	0.5851	likely_pathogenic	0.593	pathogenic	-2.089	Highly Destabilizing	0.95	D	0.747	deleterious	None	None	None	None	N
T/E	0.4796	ambiguous	0.4755	ambiguous	-1.938	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
T/F	0.1644	likely_benign	0.1882	benign	-0.809	Destabilizing	0.843	D	0.671	neutral	None	None	None	None	N
T/G	0.3861	ambiguous	0.4072	ambiguous	-1.078	Destabilizing	0.958	D	0.732	prob.delet.	None	None	None	None	N
T/H	0.234	likely_benign	0.245	benign	-1.495	Destabilizing	0.997	D	0.733	prob.delet.	None	None	None	None	N
T/I	0.0982	likely_benign	0.1146	benign	0.126	Stabilizing	0.994	D	0.755	deleterious	N	0.456696527	None	None	N
T/K	0.2903	likely_benign	0.2784	benign	-0.508	Destabilizing	0.997	D	0.747	deleterious	None	None	None	None	N
T/L	0.0923	likely_benign	0.1074	benign	0.126	Stabilizing	0.993	D	0.743	deleterious	None	None	None	None	N
T/M	0.0906	likely_benign	0.0917	benign	0.205	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
T/N	0.1606	likely_benign	0.1788	benign	-1.306	Destabilizing	0.805	D	0.7	prob.neutral	N	0.505782279	None	None	N
T/P	0.8098	likely_pathogenic	0.835	pathogenic	-0.13	Destabilizing	0.967	D	0.749	deleterious	D	0.524140024	None	None	N
T/Q	0.265	likely_benign	0.2684	benign	-1.215	Destabilizing	0.977	D	0.752	deleterious	None	None	None	None	N
T/R	0.1881	likely_benign	0.184	benign	-0.644	Destabilizing	0.938	D	0.57	neutral	None	None	None	None	N
T/S	0.108	likely_benign	0.1167	benign	-1.294	Destabilizing	0.018	N	0.314	neutral	N	0.496884447	None	None	N
T/V	0.1017	likely_benign	0.1113	benign	-0.13	Destabilizing	0.979	D	0.711	prob.delet.	None	None	None	None	N
T/W	0.5583	ambiguous	0.5677	pathogenic	-1.086	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
T/Y	0.2441	likely_benign	0.2516	benign	-0.615	Destabilizing	0.997	D	0.755	deleterious	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.