TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21564	64915;64916;64917	chr2:178584951;178584950;178584949	chr2:179449678;179449677;179449676
N2AB	19923	59992;59993;59994	chr2:178584951;178584950;178584949	chr2:179449678;179449677;179449676
N2A	18996	57211;57212;57213	chr2:178584951;178584950;178584949	chr2:179449678;179449677;179449676
N2B	12499	37720;37721;37722	chr2:178584951;178584950;178584949	chr2:179449678;179449677;179449676
Novex-1	12624	38095;38096;38097	chr2:178584951;178584950;178584949	chr2:179449678;179449677;179449676
Novex-2	12691	38296;38297;38298	chr2:178584951;178584950;178584949	chr2:179449678;179449677;179449676
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-44
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.2375
• 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
Q/L	None	None	0.801	N	0.468	0.193	0.323886383625	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
Q/A	0.2739	likely_benign	0.2491	benign	-0.657	Destabilizing	0.688	D	0.426	neutral	None	None	None	None	N
Q/C	0.6526	likely_pathogenic	0.6002	pathogenic	-0.158	Destabilizing	0.998	D	0.589	neutral	None	None	None	None	N
Q/D	0.6783	likely_pathogenic	0.6414	pathogenic	-1.289	Destabilizing	0.525	D	0.433	neutral	None	None	None	None	N
Q/E	0.108	likely_benign	0.0958	benign	-1.095	Destabilizing	0.002	N	0.095	neutral	N	0.39798689	None	None	N
Q/F	0.7769	likely_pathogenic	0.7331	pathogenic	-0.043	Destabilizing	0.991	D	0.543	neutral	None	None	None	None	N
Q/G	0.3621	ambiguous	0.3084	benign	-1.082	Destabilizing	0.915	D	0.465	neutral	None	None	None	None	N
Q/H	0.3973	ambiguous	0.375	ambiguous	-1.053	Destabilizing	0.966	D	0.456	neutral	N	0.498575171	None	None	N
Q/I	0.4113	ambiguous	0.3814	ambiguous	0.478	Stabilizing	0.974	D	0.551	neutral	None	None	None	None	N
Q/K	0.1324	likely_benign	0.1219	benign	-0.887	Destabilizing	0.454	N	0.453	neutral	N	0.460112784	None	None	N
Q/L	0.1588	likely_benign	0.1475	benign	0.478	Stabilizing	0.801	D	0.468	neutral	N	0.489222182	None	None	N
Q/M	0.374	ambiguous	0.3438	ambiguous	0.745	Stabilizing	0.991	D	0.455	neutral	None	None	None	None	N
Q/N	0.4963	ambiguous	0.4438	ambiguous	-1.459	Destabilizing	0.842	D	0.341	neutral	None	None	None	None	N
Q/P	0.6532	likely_pathogenic	0.6881	pathogenic	0.128	Stabilizing	0.891	D	0.486	neutral	N	0.455247587	None	None	N
Q/R	0.1544	likely_benign	0.1502	benign	-1.078	Destabilizing	0.801	D	0.364	neutral	N	0.481816207	None	None	N
Q/S	0.3485	ambiguous	0.3145	benign	-1.534	Destabilizing	0.688	D	0.4	neutral	None	None	None	None	N
Q/T	0.2926	likely_benign	0.2732	benign	-1.168	Destabilizing	0.842	D	0.395	neutral	None	None	None	None	N
Q/V	0.2426	likely_benign	0.2311	benign	0.128	Stabilizing	0.915	D	0.497	neutral	None	None	None	None	N
Q/W	0.7735	likely_pathogenic	0.7756	pathogenic	-0.183	Destabilizing	0.998	D	0.58	neutral	None	None	None	None	N
Q/Y	0.5962	likely_pathogenic	0.5602	ambiguous	0.116	Stabilizing	0.991	D	0.514	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.