TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5877	17854;17855;17856	chr2:178731036;178731035;178731034	chr2:179595763;179595762;179595761
N2AB	5560	16903;16904;16905	chr2:178731036;178731035;178731034	chr2:179595763;179595762;179595761
N2A	4633	14122;14123;14124	chr2:178731036;178731035;178731034	chr2:179595763;179595762;179595761
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-42
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2859
• 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	None	None	0.454	N	0.378	0.138	0.59634542923	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	0.1857	likely_benign	0.1864	benign	-1.71	Destabilizing	0.454	N	0.378	neutral	N	0.521378326	None	None	N
V/C	0.7686	likely_pathogenic	0.7722	pathogenic	-1.255	Destabilizing	0.998	D	0.517	neutral	None	None	None	None	N
V/D	0.3827	ambiguous	0.403	ambiguous	-1.839	Destabilizing	0.801	D	0.626	neutral	N	0.48080114	None	None	N
V/E	0.283	likely_benign	0.2948	benign	-1.743	Destabilizing	0.842	D	0.596	neutral	None	None	None	None	N
V/F	0.1826	likely_benign	0.1764	benign	-1.151	Destabilizing	0.934	D	0.557	neutral	D	0.522765193	None	None	N
V/G	0.2898	likely_benign	0.309	benign	-2.11	Highly Destabilizing	0.801	D	0.625	neutral	N	0.460119224	None	None	N
V/H	0.5723	likely_pathogenic	0.5695	pathogenic	-1.75	Destabilizing	0.998	D	0.611	neutral	None	None	None	None	N
V/I	0.08	likely_benign	0.0775	benign	-0.663	Destabilizing	0.012	N	0.161	neutral	N	0.50227249	None	None	N
V/K	0.4285	ambiguous	0.4351	ambiguous	-1.353	Destabilizing	0.842	D	0.595	neutral	None	None	None	None	N
V/L	0.2098	likely_benign	0.2042	benign	-0.663	Destabilizing	0.454	N	0.433	neutral	N	0.477184832	None	None	N
V/M	0.1227	likely_benign	0.1237	benign	-0.649	Destabilizing	0.949	D	0.472	neutral	None	None	None	None	N
V/N	0.283	likely_benign	0.2894	benign	-1.37	Destabilizing	0.949	D	0.615	neutral	None	None	None	None	N
V/P	0.944	likely_pathogenic	0.9488	pathogenic	-0.98	Destabilizing	0.974	D	0.594	neutral	None	None	None	None	N
V/Q	0.3382	likely_benign	0.3449	ambiguous	-1.409	Destabilizing	0.974	D	0.607	neutral	None	None	None	None	N
V/R	0.3857	ambiguous	0.3941	ambiguous	-1.01	Destabilizing	0.974	D	0.629	neutral	None	None	None	None	N
V/S	0.1905	likely_benign	0.1987	benign	-1.952	Destabilizing	0.08	N	0.306	neutral	None	None	None	None	N
V/T	0.1551	likely_benign	0.1523	benign	-1.741	Destabilizing	0.525	D	0.429	neutral	None	None	None	None	N
V/W	0.8329	likely_pathogenic	0.8401	pathogenic	-1.498	Destabilizing	0.998	D	0.655	neutral	None	None	None	None	N
V/Y	0.5172	ambiguous	0.5039	ambiguous	-1.145	Destabilizing	0.991	D	0.555	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.