TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7438	22537;22538;22539	chr2:178722475;178722474;178722473	chr2:179587202;179587201;179587200
N2AB	7121	21586;21587;21588	chr2:178722475;178722474;178722473	chr2:179587202;179587201;179587200
N2A	6194	18805;18806;18807	chr2:178722475;178722474;178722473	chr2:179587202;179587201;179587200
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: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-59
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1099
• 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
L/F	rs371114946	-1.634	0.002	N	0.297	0.321	None	gnomAD-2.1.1	2.5E-05	None	None	None	None	N	None	2.89424E-04	0	None	0	0	None	0	None	0	0	0
L/F	rs371114946	-1.634	0.002	N	0.297	0.321	None	gnomAD-3.1.2	7.23E-05	None	None	None	None	N	None	2.65457E-04	0	0	0	0	None	0	0	0	0	0
L/F	rs371114946	-1.634	0.002	N	0.297	0.321	None	gnomAD-4.0.0	1.21799E-05	None	None	None	None	N	None	2.0971E-04	0	None	0	0	None	0	0	0	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
L/A	0.7795	likely_pathogenic	0.8129	pathogenic	-2.106	Highly Destabilizing	0.617	D	0.692	prob.neutral	None	None	None	None	N
L/C	0.7895	likely_pathogenic	0.7992	pathogenic	-1.428	Destabilizing	0.992	D	0.785	deleterious	None	None	None	None	N
L/D	0.9917	likely_pathogenic	0.9941	pathogenic	-2.58	Highly Destabilizing	0.92	D	0.864	deleterious	None	None	None	None	N
L/E	0.9563	likely_pathogenic	0.964	pathogenic	-2.28	Highly Destabilizing	0.85	D	0.832	deleterious	None	None	None	None	N
L/F	0.0613	likely_benign	0.0482	benign	-1.207	Destabilizing	0.002	N	0.297	neutral	N	0.505921023	None	None	N
L/G	0.9475	likely_pathogenic	0.9596	pathogenic	-2.702	Highly Destabilizing	0.92	D	0.826	deleterious	None	None	None	None	N
L/H	0.792	likely_pathogenic	0.8233	pathogenic	-2.372	Highly Destabilizing	0.99	D	0.875	deleterious	D	0.652167902	None	None	N
L/I	0.1236	likely_benign	0.1269	benign	-0.35	Destabilizing	0.379	N	0.599	neutral	D	0.574505261	None	None	N
L/K	0.9456	likely_pathogenic	0.9548	pathogenic	-1.485	Destabilizing	0.021	N	0.638	neutral	None	None	None	None	N
L/M	0.123	likely_benign	0.1329	benign	-0.476	Destabilizing	0.127	N	0.469	neutral	None	None	None	None	N
L/N	0.9611	likely_pathogenic	0.972	pathogenic	-2.077	Highly Destabilizing	0.92	D	0.869	deleterious	None	None	None	None	N
L/P	0.9797	likely_pathogenic	0.985	pathogenic	-0.92	Destabilizing	0.963	D	0.871	deleterious	D	0.651966098	None	None	N
L/Q	0.8138	likely_pathogenic	0.8462	pathogenic	-1.761	Destabilizing	0.85	D	0.846	deleterious	None	None	None	None	N
L/R	0.8815	likely_pathogenic	0.8975	pathogenic	-1.612	Destabilizing	0.681	D	0.801	deleterious	D	0.651966098	None	None	N
L/S	0.9187	likely_pathogenic	0.9376	pathogenic	-2.721	Highly Destabilizing	0.617	D	0.767	deleterious	None	None	None	None	N
L/T	0.8505	likely_pathogenic	0.8754	pathogenic	-2.246	Highly Destabilizing	0.766	D	0.721	prob.delet.	None	None	None	None	N
L/V	0.1469	likely_benign	0.151	benign	-0.92	Destabilizing	0.201	N	0.616	neutral	D	0.599507605	None	None	N
L/W	0.4239	ambiguous	0.432	ambiguous	-1.595	Destabilizing	0.992	D	0.849	deleterious	None	None	None	None	N
L/Y	0.4977	ambiguous	0.517	ambiguous	-1.252	Destabilizing	0.447	N	0.762	deleterious	None	None	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.