TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22051	66376;66377;66378	chr2:178582305;178582304;178582303	chr2:179447032;179447031;179447030
N2AB	20410	61453;61454;61455	chr2:178582305;178582304;178582303	chr2:179447032;179447031;179447030
N2A	19483	58672;58673;58674	chr2:178582305;178582304;178582303	chr2:179447032;179447031;179447030
N2B	12986	39181;39182;39183	chr2:178582305;178582304;178582303	chr2:179447032;179447031;179447030
Novex-1	13111	39556;39557;39558	chr2:178582305;178582304;178582303	chr2:179447032;179447031;179447030
Novex-2	13178	39757;39758;39759	chr2:178582305;178582304;178582303	chr2:179447032;179447031;179447030
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: Fn3-47
• Domain position: 96
• Structural Position: 132
• Q(SASA): 1.4413
• 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/T	None	None	0.007	N	0.403	0.237	0.227934060464	gnomAD-4.0.0	1.66811E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.95074E-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
N/A	0.8663	likely_pathogenic	0.8016	pathogenic	-0.46	Destabilizing	0.587	D	0.593	neutral	None	None	None	None	N
N/C	0.883	likely_pathogenic	0.8052	pathogenic	0.216	Stabilizing	0.996	D	0.846	deleterious	None	None	None	None	N
N/D	0.2809	likely_benign	0.2407	benign	0.308	Stabilizing	0.007	N	0.38	neutral	N	0.47368038	None	None	N
N/E	0.9265	likely_pathogenic	0.8832	pathogenic	0.306	Stabilizing	0.587	D	0.657	prob.neutral	None	None	None	None	N
N/F	0.8984	likely_pathogenic	0.8865	pathogenic	-0.715	Destabilizing	0.953	D	0.741	deleterious	None	None	None	None	N
N/G	0.8989	likely_pathogenic	0.8541	pathogenic	-0.669	Destabilizing	0.74	D	0.673	prob.neutral	None	None	None	None	N
N/H	0.4347	ambiguous	0.3903	ambiguous	-0.563	Destabilizing	0.979	D	0.618	neutral	D	0.523935842	None	None	N
N/I	0.6775	likely_pathogenic	0.6084	pathogenic	0.011	Stabilizing	0.883	D	0.774	deleterious	D	0.531459247	None	None	N
N/K	0.9385	likely_pathogenic	0.8921	pathogenic	0.098	Stabilizing	0.682	D	0.667	prob.neutral	N	0.519855387	None	None	N
N/L	0.7142	likely_pathogenic	0.658	pathogenic	0.011	Stabilizing	0.833	D	0.604	neutral	None	None	None	None	N
N/M	0.7646	likely_pathogenic	0.7081	pathogenic	0.261	Stabilizing	0.996	D	0.739	deleterious	None	None	None	None	N
N/P	0.9052	likely_pathogenic	0.8903	pathogenic	-0.118	Destabilizing	0.953	D	0.757	deleterious	None	None	None	None	N
N/Q	0.9092	likely_pathogenic	0.8547	pathogenic	-0.386	Destabilizing	0.953	D	0.657	prob.neutral	None	None	None	None	N
N/R	0.965	likely_pathogenic	0.9344	pathogenic	0.13	Stabilizing	0.909	D	0.679	prob.neutral	None	None	None	None	N
N/S	0.3432	ambiguous	0.288	benign	-0.29	Destabilizing	0.518	D	0.731	deleterious	N	0.49057263	None	None	N
N/T	0.6209	likely_pathogenic	0.5185	ambiguous	-0.125	Destabilizing	0.007	N	0.403	neutral	N	0.495938377	None	None	N
N/V	0.7802	likely_pathogenic	0.695	pathogenic	-0.118	Destabilizing	0.833	D	0.634	neutral	None	None	None	None	N
N/W	0.9716	likely_pathogenic	0.9673	pathogenic	-0.644	Destabilizing	0.996	D	0.879	deleterious	None	None	None	None	N
N/Y	0.5221	ambiguous	0.4674	ambiguous	-0.392	Destabilizing	0.979	D	0.721	deleterious	N	0.488900548	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.