TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25364	76315;76316;76317	chr2:178570042;178570041;178570040	chr2:179434769;179434768;179434767
N2AB	23723	71392;71393;71394	chr2:178570042;178570041;178570040	chr2:179434769;179434768;179434767
N2A	22796	68611;68612;68613	chr2:178570042;178570041;178570040	chr2:179434769;179434768;179434767
N2B	16299	49120;49121;49122	chr2:178570042;178570041;178570040	chr2:179434769;179434768;179434767
Novex-1	16424	49495;49496;49497	chr2:178570042;178570041;178570040	chr2:179434769;179434768;179434767
Novex-2	16491	49696;49697;49698	chr2:178570042;178570041;178570040	chr2:179434769;179434768;179434767
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: Fn3-72
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.174
• 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
L/P	rs1707567452	None	0.963	N	0.659	0.48	0.776506168477	gnomAD-4.0.0	1.59225E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43312E-05	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	0.3088	likely_benign	0.3036	benign	-2.44	Highly Destabilizing	0.617	D	0.441	neutral	None	None	None	None	I
L/C	0.278	likely_benign	0.2653	benign	-1.524	Destabilizing	0.992	D	0.529	neutral	None	None	None	None	I
L/D	0.8642	likely_pathogenic	0.811	pathogenic	-2.716	Highly Destabilizing	0.972	D	0.645	neutral	None	None	None	None	I
L/E	0.5887	likely_pathogenic	0.4985	ambiguous	-2.524	Highly Destabilizing	0.92	D	0.613	neutral	None	None	None	None	I
L/F	0.0706	likely_benign	0.0669	benign	-1.535	Destabilizing	0.002	N	0.206	neutral	None	None	None	None	I
L/G	0.5778	likely_pathogenic	0.5344	ambiguous	-2.917	Highly Destabilizing	0.92	D	0.592	neutral	None	None	None	None	I
L/H	0.1966	likely_benign	0.1556	benign	-2.135	Highly Destabilizing	0.85	D	0.658	neutral	None	None	None	None	I
L/I	0.1206	likely_benign	0.1214	benign	-1.075	Destabilizing	0.447	N	0.455	neutral	None	None	None	None	I
L/K	0.4738	ambiguous	0.402	ambiguous	-2.04	Highly Destabilizing	0.92	D	0.556	neutral	None	None	None	None	I
L/M	0.0887	likely_benign	0.0933	benign	-0.823	Destabilizing	0.896	D	0.493	neutral	N	0.498626392	None	None	I
L/N	0.4865	ambiguous	0.4483	ambiguous	-2.316	Highly Destabilizing	0.92	D	0.659	neutral	None	None	None	None	I
L/P	0.9655	likely_pathogenic	0.9547	pathogenic	-1.511	Destabilizing	0.963	D	0.659	neutral	N	0.491527409	None	None	I
L/Q	0.1639	likely_benign	0.1454	benign	-2.258	Highly Destabilizing	0.963	D	0.603	neutral	N	0.520599174	None	None	I
L/R	0.3892	ambiguous	0.3192	benign	-1.611	Destabilizing	0.896	D	0.599	neutral	N	0.49102043	None	None	I
L/S	0.3539	ambiguous	0.3239	benign	-2.935	Highly Destabilizing	0.92	D	0.537	neutral	None	None	None	None	I
L/T	0.3308	likely_benign	0.3285	benign	-2.607	Highly Destabilizing	0.92	D	0.477	neutral	None	None	None	None	I
L/V	0.1063	likely_benign	0.1092	benign	-1.511	Destabilizing	0.379	N	0.459	neutral	N	0.456312835	None	None	I
L/W	0.2321	likely_benign	0.191	benign	-1.846	Destabilizing	0.977	D	0.596	neutral	None	None	None	None	I
L/Y	0.1704	likely_benign	0.1412	benign	-1.557	Destabilizing	0.005	N	0.369	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.