TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9076	27451;27452;27453	chr2:178712799;178712798;178712797	chr2:179577526;179577525;179577524
N2AB	8759	26500;26501;26502	chr2:178712799;178712798;178712797	chr2:179577526;179577525;179577524
N2A	7832	23719;23720;23721	chr2:178712799;178712798;178712797	chr2:179577526;179577525;179577524
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-76
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0695
• 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
L/V	None	None	0.981	D	0.685	0.566	0.632033471028	gnomAD-4.0.0	1.36846E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79896E-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
L/A	0.8595	likely_pathogenic	0.8985	pathogenic	-2.466	Highly Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
L/C	0.9056	likely_pathogenic	0.9272	pathogenic	-1.831	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9996	pathogenic	-3.33	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
L/E	0.9899	likely_pathogenic	0.9953	pathogenic	-3.007	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/F	0.6659	likely_pathogenic	0.722	pathogenic	-1.485	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
L/G	0.9677	likely_pathogenic	0.9836	pathogenic	-3.074	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/H	0.9858	likely_pathogenic	0.9944	pathogenic	-2.906	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/I	0.3091	likely_benign	0.2955	benign	-0.636	Destabilizing	0.91	D	0.381	neutral	None	None	None	None	N
L/K	0.9835	likely_pathogenic	0.9932	pathogenic	-1.872	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/M	0.2562	likely_benign	0.2702	benign	-0.899	Destabilizing	0.999	D	0.759	deleterious	D	0.544424364	None	None	N
L/N	0.9933	likely_pathogenic	0.9969	pathogenic	-2.603	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
L/P	0.9959	likely_pathogenic	0.9983	pathogenic	-1.237	Destabilizing	1.0	D	0.921	deleterious	D	0.565695398	None	None	N
L/Q	0.9687	likely_pathogenic	0.9853	pathogenic	-2.237	Highly Destabilizing	1.0	D	0.922	deleterious	D	0.583799653	None	None	N
L/R	0.9683	likely_pathogenic	0.986	pathogenic	-2.029	Highly Destabilizing	1.0	D	0.917	deleterious	D	0.583799653	None	None	N
L/S	0.9871	likely_pathogenic	0.9937	pathogenic	-3.133	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/T	0.945	likely_pathogenic	0.9639	pathogenic	-2.639	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
L/V	0.3389	likely_benign	0.3247	benign	-1.237	Destabilizing	0.981	D	0.685	prob.neutral	D	0.534460411	None	None	N
L/W	0.9269	likely_pathogenic	0.9673	pathogenic	-1.929	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/Y	0.9497	likely_pathogenic	0.9748	pathogenic	-1.671	Destabilizing	1.0	D	0.844	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.