TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9502	28729;28730;28731	chr2:178709815;178709814;178709813	chr2:179574542;179574541;179574540
N2AB	9185	27778;27779;27780	chr2:178709815;178709814;178709813	chr2:179574542;179574541;179574540
N2A	8258	24997;24998;24999	chr2:178709815;178709814;178709813	chr2:179574542;179574541;179574540
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: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-81
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.4912
• 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	rs368162634	-0.136	0.002	None	0.067	0.087	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/A	rs368162634	-0.136	0.002	None	0.067	0.087	None	gnomAD-4.0.0	3.0996E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.23862E-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	0.1055	likely_benign	0.0941	benign	-0.455	Destabilizing	0.002	N	0.067	neutral	None	None	None	None	I
T/C	0.6935	likely_pathogenic	0.6205	pathogenic	-0.264	Destabilizing	0.995	D	0.369	neutral	None	None	None	None	I
T/D	0.5301	ambiguous	0.4283	ambiguous	0.253	Stabilizing	0.704	D	0.3	neutral	None	None	None	None	I
T/E	0.4267	ambiguous	0.3335	benign	0.179	Stabilizing	0.704	D	0.281	neutral	None	None	None	None	I
T/F	0.3118	likely_benign	0.2461	benign	-0.934	Destabilizing	0.893	D	0.397	neutral	None	None	None	None	I
T/G	0.426	ambiguous	0.3734	ambiguous	-0.59	Destabilizing	0.329	N	0.259	neutral	None	None	None	None	I
T/H	0.3666	ambiguous	0.305	benign	-0.943	Destabilizing	0.007	N	0.247	neutral	None	None	None	None	I
T/I	0.1934	likely_benign	0.1395	benign	-0.219	Destabilizing	0.473	N	0.377	neutral	None	None	None	None	I
T/K	0.2841	likely_benign	0.2277	benign	-0.327	Destabilizing	0.642	D	0.305	neutral	None	None	None	None	I
T/L	0.1465	likely_benign	0.1257	benign	-0.219	Destabilizing	0.144	N	0.277	neutral	None	None	None	None	I
T/M	0.0805	likely_benign	0.0772	benign	0.043	Stabilizing	0.176	N	0.279	neutral	None	None	None	None	I
T/N	0.1482	likely_benign	0.1251	benign	-0.101	Destabilizing	0.704	D	0.234	neutral	None	None	None	None	I
T/P	0.3537	ambiguous	0.2925	benign	-0.269	Destabilizing	0.927	D	0.407	neutral	None	None	None	None	I
T/Q	0.3235	likely_benign	0.2833	benign	-0.356	Destabilizing	0.944	D	0.413	neutral	None	None	None	None	I
T/R	0.2297	likely_benign	0.1834	benign	-0.083	Destabilizing	0.642	D	0.396	neutral	None	None	None	None	I
T/S	0.169	likely_benign	0.1448	benign	-0.351	Destabilizing	0.029	N	0.066	neutral	None	None	None	None	I
T/V	0.1678	likely_benign	0.1332	benign	-0.269	Destabilizing	0.329	N	0.233	neutral	None	None	None	None	I
T/W	0.7122	likely_pathogenic	0.6471	pathogenic	-0.898	Destabilizing	0.995	D	0.378	neutral	None	None	None	None	I
T/Y	0.3722	ambiguous	0.3204	benign	-0.623	Destabilizing	0.893	D	0.397	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.