TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5313	16162;16163;16164	chr2:178733356;178733355;178733354	chr2:179598083;179598082;179598081
N2AB	4996	15211;15212;15213	chr2:178733356;178733355;178733354	chr2:179598083;179598082;179598081
N2A	4069	12430;12431;12432	chr2:178733356;178733355;178733354	chr2:179598083;179598082;179598081
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-36
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.8286
• 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
N/S	None	None	0.826	N	0.381	0.204	0.176091768786	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	0	0	0
N/Y	rs2080887582	None	0.996	D	0.327	0.495	0.356072328145	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.43E-05	0	0	0	0
N/Y	rs2080887582	None	0.996	D	0.327	0.495	0.356072328145	gnomAD-4.0.0	2.56226E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.13844E-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
N/A	0.5624	ambiguous	0.5725	pathogenic	-0.048	Destabilizing	0.939	D	0.379	neutral	None	None	None	None	N
N/C	0.6767	likely_pathogenic	0.6737	pathogenic	0.097	Stabilizing	0.999	D	0.395	neutral	None	None	None	None	N
N/D	0.1519	likely_benign	0.1656	benign	0.178	Stabilizing	0.015	N	0.153	neutral	N	0.440146002	None	None	N
N/E	0.5145	ambiguous	0.5474	ambiguous	0.123	Stabilizing	0.17	N	0.184	neutral	None	None	None	None	N
N/F	0.8604	likely_pathogenic	0.8641	pathogenic	-0.662	Destabilizing	0.997	D	0.337	neutral	None	None	None	None	N
N/G	0.3988	ambiguous	0.3856	ambiguous	-0.143	Destabilizing	0.927	D	0.352	neutral	None	None	None	None	N
N/H	0.205	likely_benign	0.2068	benign	-0.13	Destabilizing	0.996	D	0.297	neutral	D	0.529216062	None	None	N
N/I	0.7381	likely_pathogenic	0.7682	pathogenic	0.102	Stabilizing	0.996	D	0.341	neutral	D	0.571021809	None	None	N
N/K	0.5018	ambiguous	0.5467	ambiguous	0.12	Stabilizing	0.92	D	0.319	neutral	N	0.444327508	None	None	N
N/L	0.6589	likely_pathogenic	0.68	pathogenic	0.102	Stabilizing	0.991	D	0.345	neutral	None	None	None	None	N
N/M	0.6545	likely_pathogenic	0.6791	pathogenic	0.046	Stabilizing	0.999	D	0.341	neutral	None	None	None	None	N
N/P	0.94	likely_pathogenic	0.949	pathogenic	0.075	Stabilizing	0.997	D	0.352	neutral	None	None	None	None	N
N/Q	0.4939	ambiguous	0.5137	ambiguous	-0.256	Destabilizing	0.939	D	0.315	neutral	None	None	None	None	N
N/R	0.5811	likely_pathogenic	0.6087	pathogenic	0.183	Stabilizing	0.982	D	0.283	neutral	None	None	None	None	N
N/S	0.1747	likely_benign	0.179	benign	-0.06	Destabilizing	0.826	D	0.381	neutral	N	0.460921661	None	None	N
N/T	0.4266	ambiguous	0.4577	ambiguous	None	Stabilizing	0.959	D	0.308	neutral	N	0.502835634	None	None	N
N/V	0.7322	likely_pathogenic	0.7535	pathogenic	0.075	Stabilizing	0.991	D	0.359	neutral	None	None	None	None	N
N/W	0.9002	likely_pathogenic	0.9019	pathogenic	-0.817	Destabilizing	0.999	D	0.503	neutral	None	None	None	None	N
N/Y	0.3122	likely_benign	0.3217	benign	-0.475	Destabilizing	0.996	D	0.327	neutral	D	0.53096329	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.