TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26945	81058;81059;81060	chr2:178565299;178565298;178565297	chr2:179430026;179430025;179430024
N2AB	25304	76135;76136;76137	chr2:178565299;178565298;178565297	chr2:179430026;179430025;179430024
N2A	24377	73354;73355;73356	chr2:178565299;178565298;178565297	chr2:179430026;179430025;179430024
N2B	17880	53863;53864;53865	chr2:178565299;178565298;178565297	chr2:179430026;179430025;179430024
Novex-1	18005	54238;54239;54240	chr2:178565299;178565298;178565297	chr2:179430026;179430025;179430024
Novex-2	18072	54439;54440;54441	chr2:178565299;178565298;178565297	chr2:179430026;179430025;179430024
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-139
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.6273
• 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
D/Y	None	None	0.99	N	0.542	0.441	0.469578130381	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
D/A	0.1101	likely_benign	0.1206	benign	-0.219	Destabilizing	0.698	D	0.472	neutral	N	0.46886834	None	None	N
D/C	0.5276	ambiguous	0.5207	ambiguous	0.174	Stabilizing	0.998	D	0.623	neutral	None	None	None	None	N
D/E	0.0911	likely_benign	0.0939	benign	-0.243	Destabilizing	0.006	N	0.207	neutral	N	0.370837574	None	None	N
D/F	0.5171	ambiguous	0.5005	ambiguous	-0.38	Destabilizing	0.993	D	0.545	neutral	None	None	None	None	N
D/G	0.1272	likely_benign	0.145	benign	-0.371	Destabilizing	0.822	D	0.44	neutral	N	0.488608894	None	None	N
D/H	0.2874	likely_benign	0.2816	benign	-0.182	Destabilizing	0.97	D	0.49	neutral	N	0.503386345	None	None	N
D/I	0.2702	likely_benign	0.2703	benign	0.119	Stabilizing	0.978	D	0.533	neutral	None	None	None	None	N
D/K	0.3038	likely_benign	0.3088	benign	0.352	Stabilizing	0.019	N	0.256	neutral	None	None	None	None	N
D/L	0.3056	likely_benign	0.3185	benign	0.119	Stabilizing	0.956	D	0.439	neutral	None	None	None	None	N
D/M	0.4391	ambiguous	0.4342	ambiguous	0.301	Stabilizing	0.998	D	0.537	neutral	None	None	None	None	N
D/N	0.0904	likely_benign	0.0942	benign	0.226	Stabilizing	0.822	D	0.481	neutral	N	0.488262177	None	None	N
D/P	0.7455	likely_pathogenic	0.7628	pathogenic	0.027	Stabilizing	0.978	D	0.443	neutral	None	None	None	None	N
D/Q	0.2524	likely_benign	0.255	benign	0.224	Stabilizing	0.754	D	0.446	neutral	None	None	None	None	N
D/R	0.3839	ambiguous	0.3848	ambiguous	0.448	Stabilizing	0.915	D	0.423	neutral	None	None	None	None	N
D/S	0.1003	likely_benign	0.1056	benign	0.103	Stabilizing	0.86	D	0.455	neutral	None	None	None	None	N
D/T	0.1599	likely_benign	0.1652	benign	0.213	Stabilizing	0.86	D	0.451	neutral	None	None	None	None	N
D/V	0.1525	likely_benign	0.1578	benign	0.027	Stabilizing	0.942	D	0.439	neutral	N	0.495748297	None	None	N
D/W	0.8348	likely_pathogenic	0.8364	pathogenic	-0.327	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	N
D/Y	0.2024	likely_benign	0.1972	benign	-0.166	Destabilizing	0.99	D	0.542	neutral	N	0.46034015	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.