TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25940	78043;78044;78045	chr2:178568314;178568313;178568312	chr2:179433041;179433040;179433039
N2AB	24299	73120;73121;73122	chr2:178568314;178568313;178568312	chr2:179433041;179433040;179433039
N2A	23372	70339;70340;70341	chr2:178568314;178568313;178568312	chr2:179433041;179433040;179433039
N2B	16875	50848;50849;50850	chr2:178568314;178568313;178568312	chr2:179433041;179433040;179433039
Novex-1	17000	51223;51224;51225	chr2:178568314;178568313;178568312	chr2:179433041;179433040;179433039
Novex-2	17067	51424;51425;51426	chr2:178568314;178568313;178568312	chr2:179433041;179433040;179433039
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-76
• Domain position: 51
• Structural Position: 67
• Q(SASA): 0.4158
• Predicted PPI site: I

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	0.161	0.047	0.233150807113	gnomAD-4.0.0	1.59195E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02572E-05

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	0.1244	likely_benign	0.1446	benign	-0.829	Destabilizing	None	N	0.152	neutral	N	0.475882818	None	None	I
V/C	0.5809	likely_pathogenic	0.5759	pathogenic	-0.644	Destabilizing	0.824	D	0.571	neutral	None	None	None	None	I
V/D	0.2909	likely_benign	0.3515	ambiguous	-0.684	Destabilizing	0.317	N	0.624	neutral	N	0.454950185	None	None	I
V/E	0.2959	likely_benign	0.3235	benign	-0.786	Destabilizing	0.149	N	0.596	neutral	None	None	None	None	I
V/F	0.1787	likely_benign	0.2088	benign	-0.921	Destabilizing	0.188	N	0.605	neutral	N	0.510766183	None	None	I
V/G	0.2118	likely_benign	0.2483	benign	-1.013	Destabilizing	0.062	N	0.558	neutral	N	0.506379083	None	None	I
V/H	0.4636	ambiguous	0.5032	ambiguous	-0.549	Destabilizing	0.935	D	0.608	neutral	None	None	None	None	I
V/I	0.0639	likely_benign	0.0668	benign	-0.476	Destabilizing	None	N	0.161	neutral	N	0.460222719	None	None	I
V/K	0.3276	likely_benign	0.3469	ambiguous	-0.73	Destabilizing	0.149	N	0.59	neutral	None	None	None	None	I
V/L	0.1338	likely_benign	0.1419	benign	-0.476	Destabilizing	None	N	0.139	neutral	N	0.473151944	None	None	I
V/M	0.0948	likely_benign	0.0977	benign	-0.349	Destabilizing	0.38	N	0.518	neutral	None	None	None	None	I
V/N	0.1508	likely_benign	0.1825	benign	-0.402	Destabilizing	0.38	N	0.625	neutral	None	None	None	None	I
V/P	0.3773	ambiguous	0.4153	ambiguous	-0.558	Destabilizing	0.555	D	0.613	neutral	None	None	None	None	I
V/Q	0.2994	likely_benign	0.3118	benign	-0.684	Destabilizing	0.555	D	0.605	neutral	None	None	None	None	I
V/R	0.3204	likely_benign	0.34	benign	-0.126	Destabilizing	0.38	N	0.62	neutral	None	None	None	None	I
V/S	0.1421	likely_benign	0.1667	benign	-0.792	Destabilizing	0.081	N	0.522	neutral	None	None	None	None	I
V/T	0.0786	likely_benign	0.0922	benign	-0.796	Destabilizing	None	N	0.141	neutral	None	None	None	None	I
V/W	0.7469	likely_pathogenic	0.7716	pathogenic	-0.999	Destabilizing	0.935	D	0.623	neutral	None	None	None	None	I
V/Y	0.4383	ambiguous	0.4756	ambiguous	-0.718	Destabilizing	0.555	D	0.585	neutral	None	None	None	None	I

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.