TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8193	24802;24803;24804	chr2:178718529;178718528;178718527	chr2:179583256;179583255;179583254
N2AB	7876	23851;23852;23853	chr2:178718529;178718528;178718527	chr2:179583256;179583255;179583254
N2A	6949	21070;21071;21072	chr2:178718529;178718528;178718527	chr2:179583256;179583255;179583254
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-67
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.202
• 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/A	rs774247592	-1.495	0.454	N	0.433	0.144	0.369867359543	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.65E-05	0	0
T/A	rs774247592	-1.495	0.454	N	0.433	0.144	0.369867359543	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.41E-05	0	0	0	0
T/A	rs774247592	-1.495	0.454	N	0.433	0.144	0.369867359543	gnomAD-4.0.0	1.02488E-05	None	None	None	None	N	None	0	1.69451E-05	None	0	0	None	9.41413E-05	0	2.39316E-06	0	0
T/I	None	None	0.012	D	0.315	0.215	0.438170831126	gnomAD-4.0.0	1.59148E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85855E-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
T/A	0.1178	likely_benign	0.1054	benign	-1.235	Destabilizing	0.454	N	0.433	neutral	N	0.487240174	None	None	N
T/C	0.6621	likely_pathogenic	0.6294	pathogenic	-0.804	Destabilizing	0.998	D	0.506	neutral	None	None	None	None	N
T/D	0.7025	likely_pathogenic	0.6549	pathogenic	-0.916	Destabilizing	0.842	D	0.459	neutral	None	None	None	None	N
T/E	0.5474	ambiguous	0.4813	ambiguous	-0.781	Destabilizing	0.728	D	0.477	neutral	None	None	None	None	N
T/F	0.4499	ambiguous	0.4076	ambiguous	-0.956	Destabilizing	0.949	D	0.566	neutral	None	None	None	None	N
T/G	0.4374	ambiguous	0.3861	ambiguous	-1.601	Destabilizing	0.728	D	0.517	neutral	None	None	None	None	N
T/H	0.5054	ambiguous	0.4668	ambiguous	-1.65	Destabilizing	0.993	D	0.562	neutral	None	None	None	None	N
T/I	0.2554	likely_benign	0.2555	benign	-0.298	Destabilizing	0.012	N	0.315	neutral	D	0.527000363	None	None	N
T/K	0.4778	ambiguous	0.4084	ambiguous	-0.598	Destabilizing	0.669	D	0.477	neutral	N	0.491172849	None	None	N
T/L	0.1958	likely_benign	0.1745	benign	-0.298	Destabilizing	0.525	D	0.459	neutral	None	None	None	None	N
T/M	0.1475	likely_benign	0.1343	benign	-0.214	Destabilizing	0.949	D	0.525	neutral	None	None	None	None	N
T/N	0.2528	likely_benign	0.2403	benign	-0.976	Destabilizing	0.842	D	0.469	neutral	None	None	None	None	N
T/P	0.5346	ambiguous	0.4745	ambiguous	-0.579	Destabilizing	0.966	D	0.539	neutral	D	0.534003694	None	None	N
T/Q	0.4127	ambiguous	0.3564	ambiguous	-0.932	Destabilizing	0.325	N	0.304	neutral	None	None	None	None	N
T/R	0.3749	ambiguous	0.3162	benign	-0.597	Destabilizing	0.934	D	0.525	neutral	N	0.482150721	None	None	N
T/S	0.1615	likely_benign	0.1484	benign	-1.301	Destabilizing	0.022	N	0.169	neutral	N	0.485383027	None	None	N
T/V	0.1842	likely_benign	0.1805	benign	-0.579	Destabilizing	0.525	D	0.481	neutral	None	None	None	None	N
T/W	0.846	likely_pathogenic	0.8197	pathogenic	-0.952	Destabilizing	0.998	D	0.592	neutral	None	None	None	None	N
T/Y	0.5535	ambiguous	0.5112	ambiguous	-0.65	Destabilizing	0.991	D	0.571	neutral	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.