TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30796	92611;92612;92613	chr2:178549240;178549239;178549238	chr2:179413967;179413966;179413965
N2AB	29155	87688;87689;87690	chr2:178549240;178549239;178549238	chr2:179413967;179413966;179413965
N2A	28228	84907;84908;84909	chr2:178549240;178549239;178549238	chr2:179413967;179413966;179413965
N2B	21731	65416;65417;65418	chr2:178549240;178549239;178549238	chr2:179413967;179413966;179413965
Novex-1	21856	65791;65792;65793	chr2:178549240;178549239;178549238	chr2:179413967;179413966;179413965
Novex-2	21923	65992;65993;65994	chr2:178549240;178549239;178549238	chr2:179413967;179413966;179413965
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-112
• Domain position: 78
• Structural Position: 109
• Q(SASA): 0.1558
• 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
M/I	rs1698372447	None	0.454	N	0.745	0.203	0.488827753106	gnomAD-4.0.0	4.77336E-06	None	None	None	None	N	None	0	0	None	0	8.32131E-05	None	0	0	0	0	0
M/V	rs773266486	-1.491	0.454	N	0.599	0.192	0.480801007081	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	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
M/A	0.3711	ambiguous	0.3924	ambiguous	-2.546	Highly Destabilizing	0.688	D	0.719	prob.delet.	None	None	None	None	N
M/C	0.6627	likely_pathogenic	0.6805	pathogenic	-1.997	Destabilizing	0.998	D	0.706	prob.neutral	None	None	None	None	N
M/D	0.9372	likely_pathogenic	0.9415	pathogenic	-2.359	Highly Destabilizing	0.991	D	0.745	deleterious	None	None	None	None	N
M/E	0.6437	likely_pathogenic	0.6349	pathogenic	-2.224	Highly Destabilizing	0.991	D	0.715	prob.delet.	None	None	None	None	N
M/F	0.3209	likely_benign	0.322	benign	-1.122	Destabilizing	0.842	D	0.679	prob.neutral	None	None	None	None	N
M/G	0.6956	likely_pathogenic	0.7091	pathogenic	-2.913	Highly Destabilizing	0.991	D	0.709	prob.delet.	None	None	None	None	N
M/H	0.5049	ambiguous	0.5061	ambiguous	-2.373	Highly Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
M/I	0.5449	ambiguous	0.5703	pathogenic	-1.507	Destabilizing	0.454	N	0.745	deleterious	N	0.414063568	None	None	N
M/K	0.1821	likely_benign	0.1706	benign	-1.742	Destabilizing	0.891	D	0.689	prob.neutral	N	0.387530328	None	None	N
M/L	0.1691	likely_benign	0.182	benign	-1.507	Destabilizing	0.002	N	0.308	neutral	N	0.426550076	None	None	N
M/N	0.642	likely_pathogenic	0.6584	pathogenic	-1.824	Destabilizing	0.991	D	0.723	prob.delet.	None	None	None	None	N
M/P	0.9939	likely_pathogenic	0.9953	pathogenic	-1.837	Destabilizing	0.991	D	0.728	prob.delet.	None	None	None	None	N
M/Q	0.2359	likely_benign	0.234	benign	-1.717	Destabilizing	0.991	D	0.657	neutral	None	None	None	None	N
M/R	0.1865	likely_benign	0.1774	benign	-1.505	Destabilizing	0.966	D	0.712	prob.delet.	N	0.402979783	None	None	N
M/S	0.3493	ambiguous	0.3702	ambiguous	-2.338	Highly Destabilizing	0.915	D	0.689	prob.neutral	None	None	None	None	N
M/T	0.1881	likely_benign	0.1952	benign	-2.114	Highly Destabilizing	0.891	D	0.701	prob.neutral	N	0.396669886	None	None	N
M/V	0.1638	likely_benign	0.1646	benign	-1.837	Destabilizing	0.454	N	0.599	neutral	N	0.429974383	None	None	N
M/W	0.6635	likely_pathogenic	0.6519	pathogenic	-1.36	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	N
M/Y	0.5891	likely_pathogenic	0.5957	pathogenic	-1.43	Destabilizing	0.974	D	0.722	prob.delet.	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.