TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26676	80251;80252;80253	chr2:178566106;178566105;178566104	chr2:179430833;179430832;179430831
N2AB	25035	75328;75329;75330	chr2:178566106;178566105;178566104	chr2:179430833;179430832;179430831
N2A	24108	72547;72548;72549	chr2:178566106;178566105;178566104	chr2:179430833;179430832;179430831
N2B	17611	53056;53057;53058	chr2:178566106;178566105;178566104	chr2:179430833;179430832;179430831
Novex-1	17736	53431;53432;53433	chr2:178566106;178566105;178566104	chr2:179430833;179430832;179430831
Novex-2	17803	53632;53633;53634	chr2:178566106;178566105;178566104	chr2:179430833;179430832;179430831
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-138
• Domain position: 83
• Structural Position: 172
• Q(SASA): 0.1219
• 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/I	None	None	0.997	N	0.615	0.293	0.699463360188	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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	0.836	likely_pathogenic	0.8189	pathogenic	-1.728	Destabilizing	0.999	D	0.601	neutral	N	0.518279306	None	None	N
V/C	0.9084	likely_pathogenic	0.9142	pathogenic	-1.27	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
V/D	0.9983	likely_pathogenic	0.9977	pathogenic	-2.048	Highly Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
V/E	0.9952	likely_pathogenic	0.9935	pathogenic	-1.745	Destabilizing	1.0	D	0.898	deleterious	D	0.54194824	None	None	N
V/F	0.7105	likely_pathogenic	0.7065	pathogenic	-0.903	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/G	0.9376	likely_pathogenic	0.9333	pathogenic	-2.344	Highly Destabilizing	1.0	D	0.89	deleterious	N	0.510018918	None	None	N
V/H	0.9958	likely_pathogenic	0.9949	pathogenic	-2.224	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
V/I	0.1032	likely_benign	0.1036	benign	0.025	Stabilizing	0.997	D	0.615	neutral	N	0.463852962	None	None	N
V/K	0.9936	likely_pathogenic	0.9928	pathogenic	-1.332	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/L	0.6285	likely_pathogenic	0.633	pathogenic	0.025	Stabilizing	0.997	D	0.61	neutral	N	0.509873253	None	None	N
V/M	0.6861	likely_pathogenic	0.6678	pathogenic	-0.164	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
V/N	0.9917	likely_pathogenic	0.9892	pathogenic	-1.878	Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	N
V/P	0.9963	likely_pathogenic	0.9949	pathogenic	-0.534	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
V/Q	0.9884	likely_pathogenic	0.9857	pathogenic	-1.506	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
V/R	0.9866	likely_pathogenic	0.985	pathogenic	-1.567	Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	N
V/S	0.9493	likely_pathogenic	0.942	pathogenic	-2.543	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
V/T	0.8666	likely_pathogenic	0.8541	pathogenic	-2.057	Highly Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
V/W	0.995	likely_pathogenic	0.9952	pathogenic	-1.4	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
V/Y	0.9809	likely_pathogenic	0.9787	pathogenic	-0.973	Destabilizing	1.0	D	0.875	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.