TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5994	18205;18206;18207	chr2:178730553;178730552;178730551	chr2:179595280;179595279;179595278
N2AB	5677	17254;17255;17256	chr2:178730553;178730552;178730551	chr2:179595280;179595279;179595278
N2A	4750	14473;14474;14475	chr2:178730553;178730552;178730551	chr2:179595280;179595279;179595278
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-43
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.3281
• 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
T/S	rs751239780	-0.873	0.961	N	0.554	0.271	0.273938319068	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	2.32234E-04	0	0
T/S	rs751239780	-0.873	0.961	N	0.554	0.271	0.273938319068	gnomAD-4.0.0	7.96024E-06	None	None	None	None	N	None	0	0	None	0	0	None	9.4123E-05	0	0	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
T/A	0.084	likely_benign	0.0827	benign	-0.794	Destabilizing	0.91	D	0.557	neutral	N	0.50035248	None	None	N
T/C	0.5072	ambiguous	0.4645	ambiguous	-0.684	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
T/D	0.4436	ambiguous	0.4712	ambiguous	-1.314	Destabilizing	0.996	D	0.609	neutral	None	None	None	None	N
T/E	0.2979	likely_benign	0.3245	benign	-1.29	Destabilizing	0.97	D	0.599	neutral	None	None	None	None	N
T/F	0.2372	likely_benign	0.2263	benign	-0.938	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
T/G	0.3012	likely_benign	0.2953	benign	-1.063	Destabilizing	0.985	D	0.701	prob.neutral	None	None	None	None	N
T/H	0.2555	likely_benign	0.2466	benign	-1.45	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/I	0.1582	likely_benign	0.1593	benign	-0.161	Destabilizing	0.998	D	0.68	prob.neutral	N	0.489863974	None	None	N
T/K	0.1535	likely_benign	0.1652	benign	-0.88	Destabilizing	0.248	N	0.299	neutral	N	0.491596924	None	None	N
T/L	0.1338	likely_benign	0.133	benign	-0.161	Destabilizing	0.985	D	0.599	neutral	None	None	None	None	N
T/M	0.1057	likely_benign	0.1028	benign	0.228	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
T/N	0.161	likely_benign	0.1677	benign	-1.073	Destabilizing	0.996	D	0.579	neutral	None	None	None	None	N
T/P	0.7974	likely_pathogenic	0.8567	pathogenic	-0.34	Destabilizing	0.998	D	0.67	neutral	D	0.543518403	None	None	N
T/Q	0.191	likely_benign	0.1961	benign	-1.285	Destabilizing	0.991	D	0.651	neutral	None	None	None	None	N
T/R	0.1237	likely_benign	0.1331	benign	-0.612	Destabilizing	0.433	N	0.351	neutral	N	0.521439828	None	None	N
T/S	0.1056	likely_benign	0.1035	benign	-1.184	Destabilizing	0.961	D	0.554	neutral	N	0.466970625	None	None	N
T/V	0.1231	likely_benign	0.1199	benign	-0.34	Destabilizing	0.985	D	0.583	neutral	None	None	None	None	N
T/W	0.569	likely_pathogenic	0.5583	ambiguous	-0.956	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
T/Y	0.3114	likely_benign	0.3042	benign	-0.656	Destabilizing	0.999	D	0.775	deleterious	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.