TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27769	83530;83531;83532	chr2:178562827;178562826;178562825	chr2:179427554;179427553;179427552
N2AB	26128	78607;78608;78609	chr2:178562827;178562826;178562825	chr2:179427554;179427553;179427552
N2A	25201	75826;75827;75828	chr2:178562827;178562826;178562825	chr2:179427554;179427553;179427552
N2B	18704	56335;56336;56337	chr2:178562827;178562826;178562825	chr2:179427554;179427553;179427552
Novex-1	18829	56710;56711;56712	chr2:178562827;178562826;178562825	chr2:179427554;179427553;179427552
Novex-2	18896	56911;56912;56913	chr2:178562827;178562826;178562825	chr2:179427554;179427553;179427552
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-90
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.1705
• 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
A/S	None	None	0.958	N	0.735	0.28	0.323886383625	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
A/V	None	None	0.979	N	0.778	0.418	0.491112125781	gnomAD-4.0.0	5.47655E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.1976E-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
A/C	0.5204	ambiguous	0.52	ambiguous	-1.044	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
A/D	0.6648	likely_pathogenic	0.6826	pathogenic	-1.758	Destabilizing	0.994	D	0.847	deleterious	D	0.532311957	None	None	I
A/E	0.3849	ambiguous	0.4104	ambiguous	-1.805	Destabilizing	0.991	D	0.796	deleterious	None	None	None	None	I
A/F	0.5887	likely_pathogenic	0.5878	pathogenic	-1.242	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
A/G	0.2185	likely_benign	0.2178	benign	-1.323	Destabilizing	0.958	D	0.723	prob.delet.	D	0.532565447	None	None	I
A/H	0.6703	likely_pathogenic	0.6686	pathogenic	-1.41	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
A/I	0.4236	ambiguous	0.4457	ambiguous	-0.62	Destabilizing	0.995	D	0.811	deleterious	None	None	None	None	I
A/K	0.6258	likely_pathogenic	0.6413	pathogenic	-1.313	Destabilizing	0.991	D	0.808	deleterious	None	None	None	None	I
A/L	0.3332	likely_benign	0.3463	ambiguous	-0.62	Destabilizing	0.968	D	0.804	deleterious	None	None	None	None	I
A/M	0.3454	ambiguous	0.3603	ambiguous	-0.471	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
A/N	0.51	ambiguous	0.5109	ambiguous	-1.063	Destabilizing	0.995	D	0.851	deleterious	None	None	None	None	I
A/P	0.1425	likely_benign	0.1511	benign	-0.74	Destabilizing	0.142	N	0.522	neutral	N	0.423880704	None	None	I
A/Q	0.4143	ambiguous	0.4221	ambiguous	-1.302	Destabilizing	0.995	D	0.82	deleterious	None	None	None	None	I
A/R	0.583	likely_pathogenic	0.6025	pathogenic	-0.885	Destabilizing	0.995	D	0.811	deleterious	None	None	None	None	I
A/S	0.1127	likely_benign	0.107	benign	-1.347	Destabilizing	0.958	D	0.735	prob.delet.	N	0.521583396	None	None	I
A/T	0.1692	likely_benign	0.1775	benign	-1.32	Destabilizing	0.988	D	0.832	deleterious	N	0.50021805	None	None	I
A/V	0.22	likely_benign	0.2368	benign	-0.74	Destabilizing	0.979	D	0.778	deleterious	N	0.498078457	None	None	I
A/W	0.9086	likely_pathogenic	0.9148	pathogenic	-1.538	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
A/Y	0.6737	likely_pathogenic	0.676	pathogenic	-1.177	Destabilizing	1.0	D	0.855	deleterious	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.