TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7991	24196;24197;24198	chr2:178719419;178719418;178719417	chr2:179584146;179584145;179584144
N2AB	7674	23245;23246;23247	chr2:178719419;178719418;178719417	chr2:179584146;179584145;179584144
N2A	6747	20464;20465;20466	chr2:178719419;178719418;178719417	chr2:179584146;179584145;179584144
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: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-65
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.163
• 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/P	rs780984243	-2.023	0.999	N	0.888	0.428	0.745525825506	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	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	0.7262	likely_pathogenic	0.8345	pathogenic	-2.182	Highly Destabilizing	0.991	D	0.638	neutral	None	None	None	None	N
L/C	0.8672	likely_pathogenic	0.9305	pathogenic	-1.441	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
L/D	0.9912	likely_pathogenic	0.9969	pathogenic	-1.781	Destabilizing	0.999	D	0.889	deleterious	None	None	None	None	N
L/E	0.9408	likely_pathogenic	0.9767	pathogenic	-1.689	Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
L/F	0.5692	likely_pathogenic	0.7038	pathogenic	-1.424	Destabilizing	0.289	N	0.372	neutral	None	None	None	None	N
L/G	0.9212	likely_pathogenic	0.9645	pathogenic	-2.618	Highly Destabilizing	0.998	D	0.859	deleterious	None	None	None	None	N
L/H	0.9234	likely_pathogenic	0.9728	pathogenic	-1.879	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/I	0.2113	likely_benign	0.268	benign	-0.992	Destabilizing	0.966	D	0.531	neutral	None	None	None	None	N
L/K	0.932	likely_pathogenic	0.9712	pathogenic	-1.499	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
L/M	0.1993	likely_benign	0.2633	benign	-0.81	Destabilizing	0.997	D	0.767	deleterious	N	0.47319462	None	None	N
L/N	0.9437	likely_pathogenic	0.9769	pathogenic	-1.446	Destabilizing	0.999	D	0.888	deleterious	None	None	None	None	N
L/P	0.2935	likely_benign	0.5215	ambiguous	-1.362	Destabilizing	0.999	D	0.888	deleterious	N	0.462057011	None	None	N
L/Q	0.7759	likely_pathogenic	0.9082	pathogenic	-1.52	Destabilizing	1.0	D	0.865	deleterious	N	0.490894028	None	None	N
L/R	0.8865	likely_pathogenic	0.9512	pathogenic	-1.015	Destabilizing	0.999	D	0.858	deleterious	D	0.526937954	None	None	N
L/S	0.9263	likely_pathogenic	0.9725	pathogenic	-2.174	Highly Destabilizing	0.998	D	0.822	deleterious	None	None	None	None	N
L/T	0.7996	likely_pathogenic	0.8996	pathogenic	-1.949	Destabilizing	0.998	D	0.772	deleterious	None	None	None	None	N
L/V	0.2378	likely_benign	0.3293	benign	-1.362	Destabilizing	0.977	D	0.501	neutral	N	0.483790457	None	None	N
L/W	0.8711	likely_pathogenic	0.9443	pathogenic	-1.599	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/Y	0.9346	likely_pathogenic	0.9709	pathogenic	-1.362	Destabilizing	0.99	D	0.807	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.