TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26367	79324;79325;79326	chr2:178567033;178567032;178567031	chr2:179431760;179431759;179431758
N2AB	24726	74401;74402;74403	chr2:178567033;178567032;178567031	chr2:179431760;179431759;179431758
N2A	23799	71620;71621;71622	chr2:178567033;178567032;178567031	chr2:179431760;179431759;179431758
N2B	17302	52129;52130;52131	chr2:178567033;178567032;178567031	chr2:179431760;179431759;179431758
Novex-1	17427	52504;52505;52506	chr2:178567033;178567032;178567031	chr2:179431760;179431759;179431758
Novex-2	17494	52705;52706;52707	chr2:178567033;178567032;178567031	chr2:179431760;179431759;179431758
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-79
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.6566
• 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
Y/C	rs1317943530	0.233	0.997	N	0.718	0.356	0.46289702323	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	5.79E-05	None	0	0	None	0	None	0	0	0
Y/C	rs1317943530	0.233	0.997	N	0.718	0.356	0.46289702323	gnomAD-4.0.0	3.18317E-06	None	None	None	None	I	None	0	4.57268E-05	None	0	0	None	0	0	0	0	0
Y/H	rs772020430	0.445	0.99	N	0.515	0.369	0.346544149963	gnomAD-4.0.0	7.202E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.87507E-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
Y/A	0.9706	likely_pathogenic	0.9695	pathogenic	-0.649	Destabilizing	0.86	D	0.646	neutral	None	None	None	None	I
Y/C	0.7709	likely_pathogenic	0.7574	pathogenic	0.066	Stabilizing	0.997	D	0.718	prob.delet.	N	0.470532637	None	None	I
Y/D	0.9738	likely_pathogenic	0.9778	pathogenic	1.066	Stabilizing	0.99	D	0.699	prob.neutral	N	0.494331204	None	None	I
Y/E	0.9904	likely_pathogenic	0.9921	pathogenic	1.052	Stabilizing	0.993	D	0.69	prob.neutral	None	None	None	None	I
Y/F	0.1328	likely_benign	0.1219	benign	-0.291	Destabilizing	0.014	N	0.231	neutral	N	0.472381153	None	None	I
Y/G	0.9662	likely_pathogenic	0.9639	pathogenic	-0.839	Destabilizing	0.978	D	0.65	neutral	None	None	None	None	I
Y/H	0.7394	likely_pathogenic	0.7708	pathogenic	0.232	Stabilizing	0.99	D	0.515	neutral	N	0.469923526	None	None	I
Y/I	0.9074	likely_pathogenic	0.9012	pathogenic	-0.174	Destabilizing	0.043	N	0.398	neutral	None	None	None	None	I
Y/K	0.9843	likely_pathogenic	0.9849	pathogenic	0.244	Stabilizing	0.978	D	0.693	prob.neutral	None	None	None	None	I
Y/L	0.915	likely_pathogenic	0.8994	pathogenic	-0.174	Destabilizing	0.303	N	0.598	neutral	None	None	None	None	I
Y/M	0.9326	likely_pathogenic	0.9197	pathogenic	-0.049	Destabilizing	0.956	D	0.613	neutral	None	None	None	None	I
Y/N	0.8386	likely_pathogenic	0.8613	pathogenic	0.076	Stabilizing	0.99	D	0.694	prob.neutral	N	0.471872083	None	None	I
Y/P	0.9971	likely_pathogenic	0.9975	pathogenic	-0.313	Destabilizing	0.993	D	0.705	prob.neutral	None	None	None	None	I
Y/Q	0.9752	likely_pathogenic	0.9772	pathogenic	0.126	Stabilizing	0.993	D	0.617	neutral	None	None	None	None	I
Y/R	0.9589	likely_pathogenic	0.9594	pathogenic	0.486	Stabilizing	0.993	D	0.697	prob.neutral	None	None	None	None	I
Y/S	0.9369	likely_pathogenic	0.9379	pathogenic	-0.41	Destabilizing	0.97	D	0.631	neutral	N	0.463909592	None	None	I
Y/T	0.9748	likely_pathogenic	0.9775	pathogenic	-0.331	Destabilizing	0.956	D	0.634	neutral	None	None	None	None	I
Y/V	0.8625	likely_pathogenic	0.8498	pathogenic	-0.313	Destabilizing	0.514	D	0.591	neutral	None	None	None	None	I
Y/W	0.7216	likely_pathogenic	0.6907	pathogenic	-0.394	Destabilizing	0.998	D	0.51	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.