TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25408	76447;76448;76449	chr2:178569910;178569909;178569908	chr2:179434637;179434636;179434635
N2AB	23767	71524;71525;71526	chr2:178569910;178569909;178569908	chr2:179434637;179434636;179434635
N2A	22840	68743;68744;68745	chr2:178569910;178569909;178569908	chr2:179434637;179434636;179434635
N2B	16343	49252;49253;49254	chr2:178569910;178569909;178569908	chr2:179434637;179434636;179434635
Novex-1	16468	49627;49628;49629	chr2:178569910;178569909;178569908	chr2:179434637;179434636;179434635
Novex-2	16535	49828;49829;49830	chr2:178569910;178569909;178569908	chr2:179434637;179434636;179434635
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-73
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3539
• 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
P/H	None	None	1.0	D	0.899	0.454	0.563728453957	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
P/L	None	None	1.0	N	0.895	0.442	0.648735566516	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.1365	likely_benign	0.168	benign	-1.476	Destabilizing	1.0	D	0.838	deleterious	N	0.496561947	None	None	N
P/C	0.7237	likely_pathogenic	0.7503	pathogenic	-0.913	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/D	0.9402	likely_pathogenic	0.9665	pathogenic	-1.792	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/E	0.7521	likely_pathogenic	0.8327	pathogenic	-1.843	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/F	0.7768	likely_pathogenic	0.8375	pathogenic	-1.348	Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
P/G	0.7243	likely_pathogenic	0.7859	pathogenic	-1.737	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/H	0.5652	likely_pathogenic	0.642	pathogenic	-1.302	Destabilizing	1.0	D	0.899	deleterious	D	0.537067989	None	None	N
P/I	0.5886	likely_pathogenic	0.6814	pathogenic	-0.865	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
P/K	0.6619	likely_pathogenic	0.7437	pathogenic	-1.194	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
P/L	0.3068	likely_benign	0.3925	ambiguous	-0.865	Destabilizing	1.0	D	0.895	deleterious	N	0.513937305	None	None	N
P/M	0.5668	likely_pathogenic	0.6496	pathogenic	-0.555	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/N	0.8173	likely_pathogenic	0.8789	pathogenic	-0.923	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
P/Q	0.4367	ambiguous	0.5147	ambiguous	-1.213	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/R	0.5147	ambiguous	0.5872	pathogenic	-0.587	Destabilizing	1.0	D	0.911	deleterious	N	0.512669857	None	None	N
P/S	0.3551	ambiguous	0.454	ambiguous	-1.311	Destabilizing	1.0	D	0.863	deleterious	N	0.489196778	None	None	N
P/T	0.3859	ambiguous	0.5064	ambiguous	-1.274	Destabilizing	1.0	D	0.861	deleterious	N	0.50684696	None	None	N
P/V	0.4615	ambiguous	0.5512	ambiguous	-1.036	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/W	0.9308	likely_pathogenic	0.949	pathogenic	-1.489	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/Y	0.8043	likely_pathogenic	0.8622	pathogenic	-1.228	Destabilizing	1.0	D	0.929	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.