TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32337	97234;97235;97236	chr2:178542845;178542844;178542843	chr2:179407572;179407571;179407570
N2AB	30696	92311;92312;92313	chr2:178542845;178542844;178542843	chr2:179407572;179407571;179407570
N2A	29769	89530;89531;89532	chr2:178542845;178542844;178542843	chr2:179407572;179407571;179407570
N2B	23272	70039;70040;70041	chr2:178542845;178542844;178542843	chr2:179407572;179407571;179407570
Novex-1	23397	70414;70415;70416	chr2:178542845;178542844;178542843	chr2:179407572;179407571;179407570
Novex-2	23464	70615;70616;70617	chr2:178542845;178542844;178542843	chr2:179407572;179407571;179407570
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-154
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.4324
• 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/T	None	None	None	N	0.133	0.064	0.165133752707	gnomAD-4.0.0	1.59121E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02389E-05

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	0.3997	ambiguous	0.3548	ambiguous	-0.831	Destabilizing	0.824	D	0.413	neutral	None	None	None	None	I
A/D	0.3155	likely_benign	0.2952	benign	-0.738	Destabilizing	0.317	N	0.566	neutral	N	0.444880412	None	None	I
A/E	0.2417	likely_benign	0.2167	benign	-0.865	Destabilizing	0.149	N	0.495	neutral	None	None	None	None	I
A/F	0.3045	likely_benign	0.2677	benign	-0.864	Destabilizing	0.38	N	0.591	neutral	None	None	None	None	I
A/G	0.1569	likely_benign	0.1338	benign	-0.475	Destabilizing	0.117	N	0.371	neutral	N	0.513068274	None	None	I
A/H	0.3861	ambiguous	0.3563	ambiguous	-0.529	Destabilizing	0.935	D	0.568	neutral	None	None	None	None	I
A/I	0.1478	likely_benign	0.1393	benign	-0.298	Destabilizing	0.029	N	0.443	neutral	None	None	None	None	I
A/K	0.3507	ambiguous	0.3165	benign	-0.884	Destabilizing	0.149	N	0.497	neutral	None	None	None	None	I
A/L	0.117	likely_benign	0.106	benign	-0.298	Destabilizing	0.035	N	0.401	neutral	None	None	None	None	I
A/M	0.1478	likely_benign	0.1378	benign	-0.424	Destabilizing	0.38	N	0.509	neutral	None	None	None	None	I
A/N	0.2023	likely_benign	0.1893	benign	-0.555	Destabilizing	0.38	N	0.586	neutral	None	None	None	None	I
A/P	0.4265	ambiguous	0.4114	ambiguous	-0.288	Destabilizing	0.484	N	0.518	neutral	N	0.513241632	None	None	I
A/Q	0.25	likely_benign	0.2294	benign	-0.808	Destabilizing	0.555	D	0.53	neutral	None	None	None	None	I
A/R	0.3581	ambiguous	0.3141	benign	-0.41	Destabilizing	0.38	N	0.528	neutral	None	None	None	None	I
A/S	0.0877	likely_benign	0.0823	benign	-0.747	Destabilizing	0.062	N	0.424	neutral	N	0.428062733	None	None	I
A/T	0.0643	likely_benign	0.0643	benign	-0.79	Destabilizing	None	N	0.133	neutral	N	0.393259513	None	None	I
A/V	0.0815	likely_benign	0.0788	benign	-0.288	Destabilizing	None	N	0.126	neutral	N	0.400494917	None	None	I
A/W	0.7208	likely_pathogenic	0.6586	pathogenic	-1.051	Destabilizing	0.935	D	0.638	neutral	None	None	None	None	I
A/Y	0.4377	ambiguous	0.388	ambiguous	-0.693	Destabilizing	0.555	D	0.594	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.