TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33010	99253;99254;99255	chr2:178538801;178538800;178538799	chr2:179403528;179403527;179403526
N2AB	31369	94330;94331;94332	chr2:178538801;178538800;178538799	chr2:179403528;179403527;179403526
N2A	30442	91549;91550;91551	chr2:178538801;178538800;178538799	chr2:179403528;179403527;179403526
N2B	23945	72058;72059;72060	chr2:178538801;178538800;178538799	chr2:179403528;179403527;179403526
Novex-1	24070	72433;72434;72435	chr2:178538801;178538800;178538799	chr2:179403528;179403527;179403526
Novex-2	24137	72634;72635;72636	chr2:178538801;178538800;178538799	chr2:179403528;179403527;179403526
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-129
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.2257
• 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
I/T	None	None	0.324	N	0.379	0.308	0.587297536726	gnomAD-4.0.0	1.59692E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86854E-06	0	0
I/V	rs1419804652	None	None	N	0.083	0.052	0.28058544554	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs1419804652	None	None	N	0.083	0.052	0.28058544554	gnomAD-4.0.0	2.02987E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.20493E-06	4.69616E-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
I/A	0.312	likely_benign	0.4083	ambiguous	-1.027	Destabilizing	0.116	N	0.418	neutral	None	None	None	None	I
I/C	0.6225	likely_pathogenic	0.7054	pathogenic	-1.033	Destabilizing	0.981	D	0.321	neutral	None	None	None	None	I
I/D	0.7753	likely_pathogenic	0.8844	pathogenic	0.123	Stabilizing	0.932	D	0.489	neutral	None	None	None	None	I
I/E	0.6547	likely_pathogenic	0.7813	pathogenic	0.096	Stabilizing	0.818	D	0.467	neutral	None	None	None	None	I
I/F	0.1839	likely_benign	0.2664	benign	-0.888	Destabilizing	0.527	D	0.363	neutral	None	None	None	None	I
I/G	0.6784	likely_pathogenic	0.8035	pathogenic	-1.263	Destabilizing	0.818	D	0.454	neutral	None	None	None	None	I
I/H	0.5693	likely_pathogenic	0.7163	pathogenic	-0.662	Destabilizing	0.981	D	0.451	neutral	None	None	None	None	I
I/K	0.5084	ambiguous	0.6373	pathogenic	-0.43	Destabilizing	0.773	D	0.459	neutral	N	0.499493183	None	None	I
I/L	0.1	likely_benign	0.1547	benign	-0.489	Destabilizing	0.001	N	0.06	neutral	N	0.478424478	None	None	I
I/M	0.119	likely_benign	0.1542	benign	-0.542	Destabilizing	0.627	D	0.405	neutral	N	0.48126074	None	None	I
I/N	0.3404	ambiguous	0.502	ambiguous	-0.25	Destabilizing	0.932	D	0.485	neutral	None	None	None	None	I
I/P	0.8624	likely_pathogenic	0.9216	pathogenic	-0.636	Destabilizing	0.932	D	0.491	neutral	None	None	None	None	I
I/Q	0.4989	ambiguous	0.6415	pathogenic	-0.406	Destabilizing	0.932	D	0.465	neutral	None	None	None	None	I
I/R	0.4069	ambiguous	0.5534	ambiguous	-0.064	Destabilizing	0.773	D	0.485	neutral	N	0.48396637	None	None	I
I/S	0.3244	likely_benign	0.4305	ambiguous	-0.927	Destabilizing	0.69	D	0.421	neutral	None	None	None	None	I
I/T	0.2221	likely_benign	0.2747	benign	-0.833	Destabilizing	0.324	N	0.379	neutral	N	0.473922735	None	None	I
I/V	0.0657	likely_benign	0.0635	benign	-0.636	Destabilizing	None	N	0.083	neutral	N	0.37804684	None	None	I
I/W	0.818	likely_pathogenic	0.9122	pathogenic	-0.882	Destabilizing	0.981	D	0.594	neutral	None	None	None	None	I
I/Y	0.5468	ambiguous	0.6837	pathogenic	-0.598	Destabilizing	0.818	D	0.361	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.