TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2702	8329;8330;8331	chr2:178771223;178771222;178771221	chr2:179635950;179635949;179635948
N2AB	2702	8329;8330;8331	chr2:178771223;178771222;178771221	chr2:179635950;179635949;179635948
N2A	2702	8329;8330;8331	chr2:178771223;178771222;178771221	chr2:179635950;179635949;179635948
N2B	2656	8191;8192;8193	chr2:178771223;178771222;178771221	chr2:179635950;179635949;179635948
Novex-1	2656	8191;8192;8193	chr2:178771223;178771222;178771221	chr2:179635950;179635949;179635948
Novex-2	2656	8191;8192;8193	chr2:178771223;178771222;178771221	chr2:179635950;179635949;179635948
Novex-3	2702	8329;8330;8331	chr2:178771223;178771222;178771221	chr2:179635950;179635949;179635948

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-16
• Domain position: 82
• Structural Position: 174
• Q(SASA): 0.1044
• 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	None	None	1.0	N	0.741	0.396	0.397391247328	gnomAD-4.0.0	6.84113E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9931E-07	0	0
L/V	None	None	0.999	N	0.531	0.369	0.336155897331	gnomAD-4.0.0	6.84113E-07	None	None	None	None	N	None	0	0	None	3.82614E-05	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	0.9608	likely_pathogenic	0.9577	pathogenic	-2.722	Highly Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
L/C	0.9435	likely_pathogenic	0.9418	pathogenic	-1.847	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
L/D	0.9994	likely_pathogenic	0.9993	pathogenic	-3.289	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/E	0.9945	likely_pathogenic	0.9943	pathogenic	-3.0	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/F	0.8407	likely_pathogenic	0.8065	pathogenic	-1.624	Destabilizing	1.0	D	0.741	deleterious	N	0.500602417	None	None	N
L/G	0.9883	likely_pathogenic	0.9874	pathogenic	-3.317	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/H	0.9929	likely_pathogenic	0.991	pathogenic	-2.897	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.562220334	None	None	N
L/I	0.2861	likely_benign	0.2935	benign	-0.955	Destabilizing	0.999	D	0.553	neutral	N	0.447949257	None	None	N
L/K	0.9921	likely_pathogenic	0.9911	pathogenic	-2.064	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/M	0.4321	ambiguous	0.3878	ambiguous	-0.946	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
L/N	0.9951	likely_pathogenic	0.9949	pathogenic	-2.619	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/P	0.9971	likely_pathogenic	0.9971	pathogenic	-1.531	Destabilizing	1.0	D	0.877	deleterious	D	0.562220334	None	None	N
L/Q	0.9819	likely_pathogenic	0.9786	pathogenic	-2.362	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/R	0.9826	likely_pathogenic	0.9803	pathogenic	-1.937	Destabilizing	1.0	D	0.889	deleterious	D	0.561800443	None	None	N
L/S	0.9947	likely_pathogenic	0.9941	pathogenic	-3.261	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/T	0.9747	likely_pathogenic	0.9706	pathogenic	-2.816	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/V	0.3573	ambiguous	0.3503	ambiguous	-1.531	Destabilizing	0.999	D	0.531	neutral	N	0.338924472	None	None	N
L/W	0.9786	likely_pathogenic	0.9726	pathogenic	-2.095	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/Y	0.9796	likely_pathogenic	0.9754	pathogenic	-1.811	Destabilizing	1.0	D	0.867	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.