TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4623	14092;14093;14094	chr2:178739366;178739365;178739364	chr2:179604093;179604092;179604091
N2AB	4306	13141;13142;13143	chr2:178739366;178739365;178739364	chr2:179604093;179604092;179604091
N2A	None	None	chr2:None	chr2:None
N2B	4260	13003;13004;13005	chr2:178739366;178739365;178739364	chr2:179604093;179604092;179604091
Novex-1	4385	13378;13379;13380	chr2:178739366;178739365;178739364	chr2:179604093;179604092;179604091
Novex-2	4452	13579;13580;13581	chr2:178739366;178739365;178739364	chr2:179604093;179604092;179604091
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-29
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1013
• 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	None	N	0.253	0.092	None	gnomAD-4.0.0	1.59118E-06	None	None	None	None	N	None	0	0	None	0	2.77485E-05	None	0	0	0	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	0.2084	likely_benign	0.2385	benign	-1.98	Destabilizing	0.001	N	0.285	neutral	N	0.453818228	None	None	N
V/C	0.6334	likely_pathogenic	0.6676	pathogenic	-1.305	Destabilizing	0.935	D	0.763	deleterious	None	None	None	None	N
V/D	0.6923	likely_pathogenic	0.7581	pathogenic	-2.217	Highly Destabilizing	0.555	D	0.817	deleterious	None	None	None	None	N
V/E	0.6006	likely_pathogenic	0.662	pathogenic	-2.088	Highly Destabilizing	0.484	N	0.803	deleterious	D	0.659305299	None	None	N
V/F	0.1991	likely_benign	0.2289	benign	-1.265	Destabilizing	0.001	N	0.555	neutral	None	None	None	None	N
V/G	0.3436	ambiguous	0.3938	ambiguous	-2.436	Highly Destabilizing	0.062	N	0.755	deleterious	D	0.620731685	None	None	N
V/H	0.7239	likely_pathogenic	0.7852	pathogenic	-2.02	Highly Destabilizing	0.935	D	0.784	deleterious	None	None	None	None	N
V/I	0.0719	likely_benign	0.0729	benign	-0.753	Destabilizing	None	N	0.253	neutral	N	0.454805361	None	None	N
V/K	0.6183	likely_pathogenic	0.6841	pathogenic	-1.796	Destabilizing	0.38	N	0.803	deleterious	None	None	None	None	N
V/L	0.1905	likely_benign	0.2137	benign	-0.753	Destabilizing	0.004	N	0.557	neutral	N	0.435646263	None	None	N
V/M	0.1901	likely_benign	0.2137	benign	-0.554	Destabilizing	0.38	N	0.661	neutral	None	None	None	None	N
V/N	0.5362	ambiguous	0.6007	pathogenic	-1.826	Destabilizing	0.555	D	0.817	deleterious	None	None	None	None	N
V/P	0.8306	likely_pathogenic	0.865	pathogenic	-1.132	Destabilizing	0.555	D	0.81	deleterious	None	None	None	None	N
V/Q	0.5561	ambiguous	0.6212	pathogenic	-1.823	Destabilizing	0.555	D	0.779	deleterious	None	None	None	None	N
V/R	0.5183	ambiguous	0.5883	pathogenic	-1.382	Destabilizing	0.555	D	0.819	deleterious	None	None	None	None	N
V/S	0.3074	likely_benign	0.3536	ambiguous	-2.411	Highly Destabilizing	0.081	N	0.735	prob.delet.	None	None	None	None	N
V/T	0.2204	likely_benign	0.2443	benign	-2.156	Highly Destabilizing	0.149	N	0.7	prob.neutral	None	None	None	None	N
V/W	0.8509	likely_pathogenic	0.8802	pathogenic	-1.666	Destabilizing	0.935	D	0.775	deleterious	None	None	None	None	N
V/Y	0.6188	likely_pathogenic	0.6801	pathogenic	-1.328	Destabilizing	0.235	N	0.815	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.