TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25231	75916;75917;75918	chr2:178570441;178570440;178570439	chr2:179435168;179435167;179435166
N2AB	23590	70993;70994;70995	chr2:178570441;178570440;178570439	chr2:179435168;179435167;179435166
N2A	22663	68212;68213;68214	chr2:178570441;178570440;178570439	chr2:179435168;179435167;179435166
N2B	16166	48721;48722;48723	chr2:178570441;178570440;178570439	chr2:179435168;179435167;179435166
Novex-1	16291	49096;49097;49098	chr2:178570441;178570440;178570439	chr2:179435168;179435167;179435166
Novex-2	16358	49297;49298;49299	chr2:178570441;178570440;178570439	chr2:179435168;179435167;179435166
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: Fn3-71
• Domain position: 28
• Structural Position: 29
• Q(SASA): 0.6803
• 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
Q/H	None	None	0.151	N	0.227	0.081	0.163833314356	gnomAD-4.0.0	1.59256E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85963E-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	0.3105	likely_benign	0.3049	benign	-0.19	Destabilizing	0.985	D	0.546	neutral	None	None	None	None	I
Q/C	0.6601	likely_pathogenic	0.6747	pathogenic	0.195	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
Q/D	0.3968	ambiguous	0.3742	ambiguous	0.033	Stabilizing	0.985	D	0.477	neutral	None	None	None	None	I
Q/E	0.0869	likely_benign	0.0865	benign	-0.001	Destabilizing	0.91	D	0.422	neutral	N	0.392069356	None	None	I
Q/F	0.7158	likely_pathogenic	0.7205	pathogenic	-0.422	Destabilizing	0.996	D	0.646	neutral	None	None	None	None	I
Q/G	0.3889	ambiguous	0.3885	ambiguous	-0.368	Destabilizing	0.985	D	0.547	neutral	None	None	None	None	I
Q/H	0.2338	likely_benign	0.2285	benign	-0.314	Destabilizing	0.151	N	0.227	neutral	N	0.400304837	None	None	I
Q/I	0.5638	ambiguous	0.5403	ambiguous	0.188	Stabilizing	0.999	D	0.642	neutral	None	None	None	None	I
Q/K	0.1898	likely_benign	0.1938	benign	0.068	Stabilizing	0.961	D	0.494	neutral	N	0.458504991	None	None	I
Q/L	0.1751	likely_benign	0.1708	benign	0.188	Stabilizing	0.98	D	0.521	neutral	N	0.470183423	None	None	I
Q/M	0.4174	ambiguous	0.4157	ambiguous	0.421	Stabilizing	0.999	D	0.428	neutral	None	None	None	None	I
Q/N	0.3318	likely_benign	0.3175	benign	-0.208	Destabilizing	0.97	D	0.479	neutral	None	None	None	None	I
Q/P	0.6612	likely_pathogenic	0.6632	pathogenic	0.09	Stabilizing	0.998	D	0.508	neutral	N	0.46064122	None	None	I
Q/R	0.1831	likely_benign	0.1898	benign	0.192	Stabilizing	0.961	D	0.508	neutral	N	0.434340053	None	None	I
Q/S	0.3303	likely_benign	0.3236	benign	-0.2	Destabilizing	0.985	D	0.468	neutral	None	None	None	None	I
Q/T	0.3584	ambiguous	0.3293	benign	-0.082	Destabilizing	0.985	D	0.494	neutral	None	None	None	None	I
Q/V	0.377	ambiguous	0.3642	ambiguous	0.09	Stabilizing	0.999	D	0.492	neutral	None	None	None	None	I
Q/W	0.6145	likely_pathogenic	0.6204	pathogenic	-0.415	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
Q/Y	0.4838	ambiguous	0.492	ambiguous	-0.155	Destabilizing	0.991	D	0.495	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.