TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20636	62131;62132;62133	chr2:178589819;178589818;178589817	chr2:179454546;179454545;179454544
N2AB	18995	57208;57209;57210	chr2:178589819;178589818;178589817	chr2:179454546;179454545;179454544
N2A	18068	54427;54428;54429	chr2:178589819;178589818;178589817	chr2:179454546;179454545;179454544
N2B	11571	34936;34937;34938	chr2:178589819;178589818;178589817	chr2:179454546;179454545;179454544
Novex-1	11696	35311;35312;35313	chr2:178589819;178589818;178589817	chr2:179454546;179454545;179454544
Novex-2	11763	35512;35513;35514	chr2:178589819;178589818;178589817	chr2:179454546;179454545;179454544
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-37
• Domain position: 68
• Structural Position: 102
• Q(SASA): 0.3355
• 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
N/S	rs2154184029	None	0.042	N	0.235	0.118	0.101711395817	gnomAD-4.0.0	2.05294E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69875E-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
N/A	0.2724	likely_benign	0.2491	benign	-0.97	Destabilizing	0.104	N	0.233	neutral	None	None	None	None	I
N/C	0.1807	likely_benign	0.1833	benign	-0.09	Destabilizing	0.958	D	0.396	neutral	None	None	None	None	I
N/D	0.3266	likely_benign	0.2117	benign	-0.802	Destabilizing	None	N	0.073	neutral	N	0.476786834	None	None	I
N/E	0.4903	ambiguous	0.3489	ambiguous	-0.623	Destabilizing	0.055	N	0.205	neutral	None	None	None	None	I
N/F	0.6604	likely_pathogenic	0.6369	pathogenic	-0.514	Destabilizing	0.667	D	0.457	neutral	None	None	None	None	I
N/G	0.3765	ambiguous	0.3603	ambiguous	-1.371	Destabilizing	0.104	N	0.217	neutral	None	None	None	None	I
N/H	0.114	likely_benign	0.0979	benign	-0.864	Destabilizing	None	N	0.05	neutral	N	0.436999143	None	None	I
N/I	0.3698	ambiguous	0.332	benign	0.089	Stabilizing	0.602	D	0.481	neutral	N	0.495180655	None	None	I
N/K	0.5855	likely_pathogenic	0.446	ambiguous	-0.267	Destabilizing	0.001	N	0.087	neutral	N	0.472957156	None	None	I
N/L	0.4185	ambiguous	0.3683	ambiguous	0.089	Stabilizing	0.22	N	0.323	neutral	None	None	None	None	I
N/M	0.3976	ambiguous	0.3784	ambiguous	0.384	Stabilizing	0.859	D	0.389	neutral	None	None	None	None	I
N/P	0.9837	likely_pathogenic	0.9672	pathogenic	-0.235	Destabilizing	0.364	N	0.421	neutral	None	None	None	None	I
N/Q	0.3289	likely_benign	0.273	benign	-0.809	Destabilizing	0.22	N	0.217	neutral	None	None	None	None	I
N/R	0.5405	ambiguous	0.4073	ambiguous	-0.393	Destabilizing	None	N	0.109	neutral	None	None	None	None	I
N/S	0.0831	likely_benign	0.0817	benign	-1.122	Destabilizing	0.042	N	0.235	neutral	N	0.4776509	None	None	I
N/T	0.1306	likely_benign	0.1242	benign	-0.735	Destabilizing	0.081	N	0.2	neutral	N	0.440684448	None	None	I
N/V	0.2927	likely_benign	0.2664	benign	-0.235	Destabilizing	0.364	N	0.423	neutral	None	None	None	None	I
N/W	0.8656	likely_pathogenic	0.8152	pathogenic	-0.3	Destabilizing	0.958	D	0.421	neutral	None	None	None	None	I
N/Y	0.2241	likely_benign	0.1936	benign	-0.046	Destabilizing	0.175	N	0.421	neutral	N	0.477293813	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.