TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22209	66850;66851;66852	chr2:178581643;178581642;178581641	chr2:179446370;179446369;179446368
N2AB	20568	61927;61928;61929	chr2:178581643;178581642;178581641	chr2:179446370;179446369;179446368
N2A	19641	59146;59147;59148	chr2:178581643;178581642;178581641	chr2:179446370;179446369;179446368
N2B	13144	39655;39656;39657	chr2:178581643;178581642;178581641	chr2:179446370;179446369;179446368
Novex-1	13269	40030;40031;40032	chr2:178581643;178581642;178581641	chr2:179446370;179446369;179446368
Novex-2	13336	40231;40232;40233	chr2:178581643;178581642;178581641	chr2:179446370;179446369;179446368
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-49
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.4534
• 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
P/L	rs779009635	-0.138	0.976	N	0.645	0.436	0.711619551443	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
P/L	rs779009635	-0.138	0.976	N	0.645	0.436	0.711619551443	gnomAD-4.0.0	2.05388E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69949E-06	0	0
P/T	None	None	0.988	N	0.565	0.354	0.500868654924	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.2848	likely_benign	0.2794	benign	-0.345	Destabilizing	0.067	N	0.282	neutral	N	0.515289355	None	None	I
P/C	0.9161	likely_pathogenic	0.9219	pathogenic	-0.786	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
P/D	0.9338	likely_pathogenic	0.9336	pathogenic	-0.402	Destabilizing	0.995	D	0.607	neutral	None	None	None	None	I
P/E	0.8293	likely_pathogenic	0.8244	pathogenic	-0.516	Destabilizing	0.991	D	0.565	neutral	None	None	None	None	I
P/F	0.9421	likely_pathogenic	0.9472	pathogenic	-0.733	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
P/G	0.736	likely_pathogenic	0.7327	pathogenic	-0.402	Destabilizing	0.938	D	0.523	neutral	None	None	None	None	I
P/H	0.7486	likely_pathogenic	0.763	pathogenic	-0.005	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	I
P/I	0.808	likely_pathogenic	0.8118	pathogenic	-0.334	Destabilizing	0.991	D	0.695	prob.neutral	None	None	None	None	I
P/K	0.8496	likely_pathogenic	0.8568	pathogenic	-0.409	Destabilizing	0.991	D	0.568	neutral	None	None	None	None	I
P/L	0.5318	ambiguous	0.5387	ambiguous	-0.334	Destabilizing	0.976	D	0.645	neutral	N	0.499631712	None	None	I
P/M	0.8523	likely_pathogenic	0.8537	pathogenic	-0.6	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
P/N	0.8953	likely_pathogenic	0.8921	pathogenic	-0.199	Destabilizing	0.995	D	0.659	neutral	None	None	None	None	I
P/Q	0.6784	likely_pathogenic	0.675	pathogenic	-0.409	Destabilizing	0.994	D	0.613	neutral	N	0.472310745	None	None	I
P/R	0.741	likely_pathogenic	0.7537	pathogenic	0.035	Stabilizing	0.994	D	0.643	neutral	N	0.481273967	None	None	I
P/S	0.5509	ambiguous	0.5441	ambiguous	-0.495	Destabilizing	0.919	D	0.511	neutral	N	0.513921131	None	None	I
P/T	0.5011	ambiguous	0.4935	ambiguous	-0.52	Destabilizing	0.988	D	0.565	neutral	N	0.517001509	None	None	I
P/V	0.642	likely_pathogenic	0.6512	pathogenic	-0.311	Destabilizing	0.982	D	0.583	neutral	None	None	None	None	I
P/W	0.9682	likely_pathogenic	0.9733	pathogenic	-0.79	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
P/Y	0.9129	likely_pathogenic	0.9199	pathogenic	-0.519	Destabilizing	1.0	D	0.711	prob.delet.	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.