TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28306	85141;85142;85143	chr2:178561216;178561215;178561214	chr2:179425943;179425942;179425941
N2AB	26665	80218;80219;80220	chr2:178561216;178561215;178561214	chr2:179425943;179425942;179425941
N2A	25738	77437;77438;77439	chr2:178561216;178561215;178561214	chr2:179425943;179425942;179425941
N2B	19241	57946;57947;57948	chr2:178561216;178561215;178561214	chr2:179425943;179425942;179425941
Novex-1	19366	58321;58322;58323	chr2:178561216;178561215;178561214	chr2:179425943;179425942;179425941
Novex-2	19433	58522;58523;58524	chr2:178561216;178561215;178561214	chr2:179425943;179425942;179425941
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: Fn3-94
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.4411
• 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/D	rs758424234	-0.518	0.581	N	0.491	0.356	0.232513804876	gnomAD-2.1.1	7.65E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.20915E-04	None	0	0	0
N/D	rs758424234	-0.518	0.581	N	0.491	0.356	0.232513804876	gnomAD-4.0.0	3.48997E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.91263E-04	0
N/H	None	None	0.968	N	0.707	0.455	0.269111216191	gnomAD-4.0.0	6.84308E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99447E-07	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	0.3174	likely_benign	0.3003	benign	-0.415	Destabilizing	0.48	N	0.61	neutral	None	None	None	None	N
N/C	0.4287	ambiguous	0.4265	ambiguous	0.34	Stabilizing	0.98	D	0.819	deleterious	None	None	None	None	N
N/D	0.3271	likely_benign	0.2992	benign	0.098	Stabilizing	0.581	D	0.491	neutral	N	0.51876959	None	None	N
N/E	0.7447	likely_pathogenic	0.7088	pathogenic	0.061	Stabilizing	0.648	D	0.579	neutral	None	None	None	None	N
N/F	0.7062	likely_pathogenic	0.7056	pathogenic	-0.763	Destabilizing	0.929	D	0.841	deleterious	None	None	None	None	N
N/G	0.444	ambiguous	0.4295	ambiguous	-0.588	Destabilizing	0.648	D	0.489	neutral	None	None	None	None	N
N/H	0.2149	likely_benign	0.205	benign	-0.61	Destabilizing	0.968	D	0.707	prob.neutral	N	0.472066801	None	None	N
N/I	0.2728	likely_benign	0.2589	benign	-0.044	Destabilizing	0.709	D	0.833	deleterious	N	0.470091791	None	None	N
N/K	0.6777	likely_pathogenic	0.6546	pathogenic	0.132	Stabilizing	0.581	D	0.596	neutral	N	0.506877728	None	None	N
N/L	0.299	likely_benign	0.2865	benign	-0.044	Destabilizing	0.764	D	0.729	prob.delet.	None	None	None	None	N
N/M	0.4261	ambiguous	0.4081	ambiguous	0.386	Stabilizing	0.98	D	0.789	deleterious	None	None	None	None	N
N/P	0.5548	ambiguous	0.5085	ambiguous	-0.141	Destabilizing	0.929	D	0.805	deleterious	None	None	None	None	N
N/Q	0.6109	likely_pathogenic	0.5858	pathogenic	-0.371	Destabilizing	0.929	D	0.715	prob.delet.	None	None	None	None	N
N/R	0.6673	likely_pathogenic	0.6482	pathogenic	0.206	Stabilizing	0.866	D	0.697	prob.neutral	None	None	None	None	N
N/S	0.1115	likely_benign	0.1125	benign	-0.132	Destabilizing	0.41	N	0.455	neutral	D	0.523116617	None	None	N
N/T	0.1888	likely_benign	0.1817	benign	-0.022	Destabilizing	0.004	N	0.316	neutral	N	0.50430157	None	None	N
N/V	0.2383	likely_benign	0.2247	benign	-0.141	Destabilizing	0.764	D	0.749	deleterious	None	None	None	None	N
N/W	0.8964	likely_pathogenic	0.8886	pathogenic	-0.702	Destabilizing	0.993	D	0.809	deleterious	None	None	None	None	N
N/Y	0.3009	likely_benign	0.2958	benign	-0.448	Destabilizing	0.908	D	0.824	deleterious	N	0.500869025	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.