TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9484	28675;28676;28677	chr2:178710647;178710646;178710645	chr2:179575374;179575373;179575372
N2AB	9167	27724;27725;27726	chr2:178710647;178710646;178710645	chr2:179575374;179575373;179575372
N2A	8240	24943;24944;24945	chr2:178710647;178710646;178710645	chr2:179575374;179575373;179575372
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-80
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.1129
• 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	rs1378540444	None	0.999	None	0.885	0.667	0.859033133088	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/P	rs1378540444	None	0.999	None	0.885	0.667	0.859033133088	gnomAD-4.0.0	2.57691E-06	None	None	None	None	N	None	1.69538E-05	0	None	0	0	None	0	0	2.40781E-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
L/A	0.8767	likely_pathogenic	0.9448	pathogenic	-3.031	Highly Destabilizing	0.983	D	0.727	prob.delet.	None	None	None	None	N
L/C	0.8712	likely_pathogenic	0.9165	pathogenic	-2.57	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
L/D	0.9977	likely_pathogenic	0.999	pathogenic	-3.478	Highly Destabilizing	0.999	D	0.884	deleterious	None	None	None	None	N
L/E	0.9864	likely_pathogenic	0.9935	pathogenic	-3.217	Highly Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
L/F	0.4874	ambiguous	0.5815	pathogenic	-1.867	Destabilizing	0.998	D	0.762	deleterious	None	None	None	None	N
L/G	0.9492	likely_pathogenic	0.9852	pathogenic	-3.622	Highly Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
L/H	0.9714	likely_pathogenic	0.9877	pathogenic	-3.024	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/I	0.1845	likely_benign	0.2169	benign	-1.286	Destabilizing	0.437	N	0.351	neutral	None	None	None	None	N
L/K	0.9761	likely_pathogenic	0.9907	pathogenic	-2.37	Highly Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	N
L/M	0.2342	likely_benign	0.3052	benign	-1.379	Destabilizing	0.997	D	0.726	prob.delet.	None	None	None	None	N
L/N	0.9845	likely_pathogenic	0.9941	pathogenic	-2.849	Highly Destabilizing	0.999	D	0.897	deleterious	None	None	None	None	N
L/P	0.9904	likely_pathogenic	0.9962	pathogenic	-1.853	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
L/Q	0.9413	likely_pathogenic	0.9765	pathogenic	-2.66	Highly Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	N
L/R	0.957	likely_pathogenic	0.9804	pathogenic	-2.089	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
L/S	0.9799	likely_pathogenic	0.992	pathogenic	-3.584	Highly Destabilizing	0.998	D	0.879	deleterious	None	None	None	None	N
L/T	0.93	likely_pathogenic	0.9658	pathogenic	-3.165	Highly Destabilizing	0.995	D	0.819	deleterious	None	None	None	None	N
L/V	0.2298	likely_benign	0.2454	benign	-1.853	Destabilizing	0.37	N	0.341	neutral	None	None	None	None	N
L/W	0.8794	likely_pathogenic	0.9275	pathogenic	-2.252	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
L/Y	0.9122	likely_pathogenic	0.95	pathogenic	-2.044	Highly Destabilizing	0.999	D	0.805	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.