TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22147	66664;66665;66666	chr2:178581930;178581929;178581928	chr2:179446657;179446656;179446655
N2AB	20506	61741;61742;61743	chr2:178581930;178581929;178581928	chr2:179446657;179446656;179446655
N2A	19579	58960;58961;58962	chr2:178581930;178581929;178581928	chr2:179446657;179446656;179446655
N2B	13082	39469;39470;39471	chr2:178581930;178581929;178581928	chr2:179446657;179446656;179446655
Novex-1	13207	39844;39845;39846	chr2:178581930;178581929;178581928	chr2:179446657;179446656;179446655
Novex-2	13274	40045;40046;40047	chr2:178581930;178581929;178581928	chr2:179446657;179446656;179446655
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-48
• Domain position: 93
• Structural Position: 126
• Q(SASA): 0.3357
• 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
A/P	rs773148853	-0.43	0.128	N	0.433	0.278	0.377451072189	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
A/P	rs773148853	-0.43	0.128	N	0.433	0.278	0.377451072189	gnomAD-4.0.0	1.59268E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43308E-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
A/C	0.5793	likely_pathogenic	0.6075	pathogenic	-0.707	Destabilizing	1.0	D	0.659	prob.neutral	None	None	None	None	N
A/D	0.6531	likely_pathogenic	0.6996	pathogenic	-0.894	Destabilizing	0.993	D	0.782	deleterious	N	0.484434881	None	None	N
A/E	0.4756	ambiguous	0.5115	ambiguous	-0.993	Destabilizing	0.995	D	0.65	prob.neutral	None	None	None	None	N
A/F	0.5388	ambiguous	0.5702	pathogenic	-0.943	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
A/G	0.1424	likely_benign	0.1667	benign	-0.816	Destabilizing	0.06	N	0.313	neutral	N	0.506734161	None	None	N
A/H	0.6648	likely_pathogenic	0.6923	pathogenic	-0.842	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
A/I	0.4455	ambiguous	0.4468	ambiguous	-0.389	Destabilizing	0.998	D	0.738	deleterious	None	None	None	None	N
A/K	0.6198	likely_pathogenic	0.6776	pathogenic	-1.027	Destabilizing	0.995	D	0.653	prob.neutral	None	None	None	None	N
A/L	0.3486	ambiguous	0.3694	ambiguous	-0.389	Destabilizing	0.995	D	0.665	prob.neutral	None	None	None	None	N
A/M	0.4117	ambiguous	0.4215	ambiguous	-0.346	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
A/N	0.4907	ambiguous	0.5153	ambiguous	-0.62	Destabilizing	0.995	D	0.809	deleterious	None	None	None	None	N
A/P	0.115	likely_benign	0.1127	benign	-0.438	Destabilizing	0.128	N	0.433	neutral	N	0.42921474	None	None	N
A/Q	0.4951	ambiguous	0.5231	ambiguous	-0.876	Destabilizing	0.998	D	0.721	deleterious	None	None	None	None	N
A/R	0.5921	likely_pathogenic	0.6466	pathogenic	-0.527	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
A/S	0.1415	likely_benign	0.1429	benign	-0.877	Destabilizing	0.953	D	0.483	neutral	N	0.481566357	None	None	N
A/T	0.1823	likely_benign	0.1891	benign	-0.896	Destabilizing	0.993	D	0.626	neutral	N	0.498978682	None	None	N
A/V	0.2465	likely_benign	0.2518	benign	-0.438	Destabilizing	0.976	D	0.605	neutral	N	0.492322069	None	None	N
A/W	0.8478	likely_pathogenic	0.8731	pathogenic	-1.163	Destabilizing	1.0	D	0.737	deleterious	None	None	None	None	N
A/Y	0.6378	likely_pathogenic	0.6643	pathogenic	-0.812	Destabilizing	1.0	D	0.793	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.