TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5775	17548;17549;17550	chr2:178731443;178731442;178731441	chr2:179596170;179596169;179596168
N2AB	5458	16597;16598;16599	chr2:178731443;178731442;178731441	chr2:179596170;179596169;179596168
N2A	4531	13816;13817;13818	chr2:178731443;178731442;178731441	chr2:179596170;179596169;179596168
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: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-41
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.3794
• 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	rs1347227022	-0.294	0.549	N	0.373	0.144	0.126345400529	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	2.87687E-04	0	0
N/S	rs1347227022	-0.294	0.549	N	0.373	0.144	0.126345400529	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.42E-05	0	0	0	0
N/S	rs1347227022	-0.294	0.549	N	0.373	0.144	0.126345400529	gnomAD-4.0.0	5.1246E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.27569E-05	0	0	0	0
N/T	None	None	0.712	N	0.388	0.149	0.186928172975	gnomAD-4.0.0	4.77395E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71647E-06	1.43279E-05	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	0.1877	likely_benign	0.1993	benign	-0.536	Destabilizing	0.617	D	0.377	neutral	None	None	None	None	N
N/C	0.2533	likely_benign	0.2635	benign	0.385	Stabilizing	0.992	D	0.556	neutral	None	None	None	None	N
N/D	0.1241	likely_benign	0.122	benign	-0.337	Destabilizing	0.549	D	0.383	neutral	N	0.491955843	None	None	N
N/E	0.351	ambiguous	0.3567	ambiguous	-0.336	Destabilizing	0.447	N	0.341	neutral	None	None	None	None	N
N/F	0.4263	ambiguous	0.4605	ambiguous	-0.763	Destabilizing	0.85	D	0.505	neutral	None	None	None	None	N
N/G	0.2361	likely_benign	0.2548	benign	-0.771	Destabilizing	0.005	N	0.152	neutral	None	None	None	None	N
N/H	0.0845	likely_benign	0.0882	benign	-0.858	Destabilizing	0.004	N	0.221	neutral	N	0.45037858	None	None	N
N/I	0.2167	likely_benign	0.2331	benign	0.013	Stabilizing	0.896	D	0.5	neutral	N	0.495612224	None	None	N
N/K	0.2172	likely_benign	0.2328	benign	-0.045	Destabilizing	0.549	D	0.38	neutral	N	0.455666969	None	None	N
N/L	0.2309	likely_benign	0.2498	benign	0.013	Stabilizing	0.85	D	0.484	neutral	None	None	None	None	N
N/M	0.2969	likely_benign	0.3291	benign	0.624	Stabilizing	0.992	D	0.448	neutral	None	None	None	None	N
N/P	0.7584	likely_pathogenic	0.7849	pathogenic	-0.142	Destabilizing	0.012	N	0.328	neutral	None	None	None	None	N
N/Q	0.2663	likely_benign	0.2826	benign	-0.588	Destabilizing	0.85	D	0.405	neutral	None	None	None	None	N
N/R	0.2257	likely_benign	0.2336	benign	-0.005	Destabilizing	0.85	D	0.39	neutral	None	None	None	None	N
N/S	0.0793	likely_benign	0.0837	benign	-0.345	Destabilizing	0.549	D	0.373	neutral	N	0.484144437	None	None	N
N/T	0.1113	likely_benign	0.1181	benign	-0.185	Destabilizing	0.712	D	0.388	neutral	N	0.513947269	None	None	N
N/V	0.2251	likely_benign	0.241	benign	-0.142	Destabilizing	0.92	D	0.498	neutral	None	None	None	None	N
N/W	0.7243	likely_pathogenic	0.747	pathogenic	-0.668	Destabilizing	0.992	D	0.595	neutral	None	None	None	None	N
N/Y	0.1511	likely_benign	0.1563	benign	-0.423	Destabilizing	0.681	D	0.459	neutral	N	0.503423631	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.