TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17955	54088;54089;54090	chr2:178605432;178605431;178605430	chr2:179470159;179470158;179470157
N2AB	16314	49165;49166;49167	chr2:178605432;178605431;178605430	chr2:179470159;179470158;179470157
N2A	15387	46384;46385;46386	chr2:178605432;178605431;178605430	chr2:179470159;179470158;179470157
N2B	8890	26893;26894;26895	chr2:178605432;178605431;178605430	chr2:179470159;179470158;179470157
Novex-1	9015	27268;27269;27270	chr2:178605432;178605431;178605430	chr2:179470159;179470158;179470157
Novex-2	9082	27469;27470;27471	chr2:178605432;178605431;178605430	chr2:179470159;179470158;179470157
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-18
• Domain position: 94
• Structural Position: 127
• Q(SASA): 0.0904
• 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
V/A	rs747319436	None	0.996	N	0.552	0.179	0.583177444714	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07383E-04	0
V/A	rs747319436	None	0.996	N	0.552	0.179	0.583177444714	gnomAD-4.0.0	3.91004E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.12394E-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
V/A	0.7781	likely_pathogenic	0.7919	pathogenic	-1.37	Destabilizing	0.996	D	0.552	neutral	N	0.46509768	None	None	N
V/C	0.9352	likely_pathogenic	0.9409	pathogenic	-0.87	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
V/D	0.9427	likely_pathogenic	0.9495	pathogenic	-1.367	Destabilizing	1.0	D	0.899	deleterious	N	0.466111638	None	None	N
V/E	0.8944	likely_pathogenic	0.896	pathogenic	-1.381	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
V/F	0.6074	likely_pathogenic	0.6231	pathogenic	-1.057	Destabilizing	0.999	D	0.86	deleterious	N	0.465351169	None	None	N
V/G	0.8448	likely_pathogenic	0.8509	pathogenic	-1.671	Destabilizing	1.0	D	0.899	deleterious	N	0.466111638	None	None	N
V/H	0.949	likely_pathogenic	0.958	pathogenic	-1.2	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
V/I	0.1157	likely_benign	0.1308	benign	-0.651	Destabilizing	0.603	D	0.231	neutral	N	0.463830232	None	None	N
V/K	0.9236	likely_pathogenic	0.9247	pathogenic	-1.298	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/L	0.5883	likely_pathogenic	0.6233	pathogenic	-0.651	Destabilizing	0.959	D	0.569	neutral	N	0.464083722	None	None	N
V/M	0.5175	ambiguous	0.5434	ambiguous	-0.447	Destabilizing	0.999	D	0.737	deleterious	None	None	None	None	N
V/N	0.8064	likely_pathogenic	0.8607	pathogenic	-1.064	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
V/P	0.9381	likely_pathogenic	0.9338	pathogenic	-0.856	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
V/Q	0.8698	likely_pathogenic	0.8882	pathogenic	-1.25	Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
V/R	0.8843	likely_pathogenic	0.89	pathogenic	-0.702	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
V/S	0.8133	likely_pathogenic	0.837	pathogenic	-1.524	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/T	0.6914	likely_pathogenic	0.7131	pathogenic	-1.435	Destabilizing	0.997	D	0.593	neutral	None	None	None	None	N
V/W	0.977	likely_pathogenic	0.9805	pathogenic	-1.261	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
V/Y	0.9024	likely_pathogenic	0.9138	pathogenic	-0.985	Destabilizing	1.0	D	0.851	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.