TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13827	41704;41705;41706	chr2:178636092;178636091;178636090	chr2:179500819;179500818;179500817
N2AB	12186	36781;36782;36783	chr2:178636092;178636091;178636090	chr2:179500819;179500818;179500817
N2A	11259	34000;34001;34002	chr2:178636092;178636091;178636090	chr2:179500819;179500818;179500817
N2B	4762	14509;14510;14511	chr2:178636092;178636091;178636090	chr2:179500819;179500818;179500817
Novex-1	4887	14884;14885;14886	chr2:178636092;178636091;178636090	chr2:179500819;179500818;179500817
Novex-2	4954	15085;15086;15087	chr2:178636092;178636091;178636090	chr2:179500819;179500818;179500817
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-88
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.2555
• 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/E	None	None	0.27	N	0.335	0.18	0.296329037015	gnomAD-4.0.0	4.79082E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29744E-06	0	0
V/G	None	None	0.27	N	0.381	0.185	0.369682402691	gnomAD-4.0.0	6.84403E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99635E-07	0	0
V/L	None	None	0.139	N	0.197	0.043	0.24896430686	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
V/A	0.3521	ambiguous	0.4105	ambiguous	-1.237	Destabilizing	0.001	N	0.066	neutral	N	0.341613636	None	None	N
V/C	0.8589	likely_pathogenic	0.8763	pathogenic	-1.029	Destabilizing	0.981	D	0.382	neutral	None	None	None	None	N
V/D	0.6875	likely_pathogenic	0.7785	pathogenic	-0.835	Destabilizing	0.704	D	0.487	neutral	None	None	None	None	N
V/E	0.4883	ambiguous	0.5762	pathogenic	-0.874	Destabilizing	0.27	N	0.335	neutral	N	0.351543553	None	None	N
V/F	0.2104	likely_benign	0.2824	benign	-1.079	Destabilizing	0.944	D	0.527	neutral	None	None	None	None	N
V/G	0.4962	ambiguous	0.5891	pathogenic	-1.503	Destabilizing	0.27	N	0.381	neutral	N	0.350087053	None	None	N
V/H	0.7362	likely_pathogenic	0.7848	pathogenic	-0.995	Destabilizing	0.944	D	0.517	neutral	None	None	None	None	N
V/I	0.0859	likely_benign	0.0887	benign	-0.631	Destabilizing	0.495	N	0.273	neutral	None	None	None	None	N
V/K	0.5725	likely_pathogenic	0.6648	pathogenic	-0.947	Destabilizing	0.329	N	0.349	neutral	None	None	None	None	N
V/L	0.2547	likely_benign	0.3169	benign	-0.631	Destabilizing	0.139	N	0.197	neutral	N	0.349375178	None	None	N
V/M	0.1792	likely_benign	0.2283	benign	-0.545	Destabilizing	0.975	D	0.382	neutral	N	0.347400505	None	None	N
V/N	0.4712	ambiguous	0.5366	ambiguous	-0.724	Destabilizing	0.704	D	0.525	neutral	None	None	None	None	N
V/P	0.9345	likely_pathogenic	0.9628	pathogenic	-0.797	Destabilizing	0.828	D	0.499	neutral	None	None	None	None	N
V/Q	0.4717	ambiguous	0.5227	ambiguous	-0.941	Destabilizing	0.037	N	0.225	neutral	None	None	None	None	N
V/R	0.5135	ambiguous	0.6228	pathogenic	-0.434	Destabilizing	0.704	D	0.528	neutral	None	None	None	None	N
V/S	0.3558	ambiguous	0.4138	ambiguous	-1.266	Destabilizing	0.037	N	0.239	neutral	None	None	None	None	N
V/T	0.3033	likely_benign	0.3377	benign	-1.193	Destabilizing	0.013	N	0.104	neutral	None	None	None	None	N
V/W	0.9134	likely_pathogenic	0.949	pathogenic	-1.178	Destabilizing	0.995	D	0.545	neutral	None	None	None	None	N
V/Y	0.6825	likely_pathogenic	0.7646	pathogenic	-0.884	Destabilizing	0.981	D	0.527	neutral	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.