TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25372	76339;76340;76341	chr2:178570018;178570017;178570016	chr2:179434745;179434744;179434743
N2AB	23731	71416;71417;71418	chr2:178570018;178570017;178570016	chr2:179434745;179434744;179434743
N2A	22804	68635;68636;68637	chr2:178570018;178570017;178570016	chr2:179434745;179434744;179434743
N2B	16307	49144;49145;49146	chr2:178570018;178570017;178570016	chr2:179434745;179434744;179434743
Novex-1	16432	49519;49520;49521	chr2:178570018;178570017;178570016	chr2:179434745;179434744;179434743
Novex-2	16499	49720;49721;49722	chr2:178570018;178570017;178570016	chr2:179434745;179434744;179434743
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: Fn3-72
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.6203
• 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/S	None	None	0.028	N	0.269	0.091	0.154104182512	gnomAD-4.0.0	1.36893E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99666E-07	1.1599E-05	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	0.2525	likely_benign	0.2647	benign	-0.525	Destabilizing	0.373	N	0.523	neutral	None	None	None	None	N
N/C	0.276	likely_benign	0.3011	benign	0.409	Stabilizing	0.996	D	0.587	neutral	None	None	None	None	N
N/D	0.112	likely_benign	0.106	benign	-0.36	Destabilizing	0.684	D	0.379	neutral	N	0.423549843	None	None	N
N/E	0.3401	ambiguous	0.3306	benign	-0.35	Destabilizing	0.742	D	0.405	neutral	None	None	None	None	N
N/F	0.469	ambiguous	0.4904	ambiguous	-0.58	Destabilizing	0.91	D	0.593	neutral	None	None	None	None	N
N/G	0.1586	likely_benign	0.1639	benign	-0.78	Destabilizing	0.004	N	0.169	neutral	None	None	None	None	N
N/H	0.1093	likely_benign	0.1039	benign	-0.81	Destabilizing	0.979	D	0.432	neutral	N	0.515651927	None	None	N
N/I	0.413	ambiguous	0.427	ambiguous	0.087	Stabilizing	0.792	D	0.589	neutral	N	0.50267945	None	None	N
N/K	0.2648	likely_benign	0.2404	benign	-0.25	Destabilizing	0.684	D	0.405	neutral	N	0.506397726	None	None	N
N/L	0.3266	likely_benign	0.3336	benign	0.087	Stabilizing	0.59	D	0.542	neutral	None	None	None	None	N
N/M	0.3508	ambiguous	0.3637	ambiguous	0.595	Stabilizing	0.373	N	0.549	neutral	None	None	None	None	N
N/P	0.8595	likely_pathogenic	0.854	pathogenic	-0.089	Destabilizing	0.953	D	0.581	neutral	None	None	None	None	N
N/Q	0.2847	likely_benign	0.2718	benign	-0.618	Destabilizing	0.953	D	0.411	neutral	None	None	None	None	N
N/R	0.3379	likely_benign	0.3261	benign	-0.21	Destabilizing	0.91	D	0.409	neutral	None	None	None	None	N
N/S	0.1008	likely_benign	0.1079	benign	-0.429	Destabilizing	0.028	N	0.269	neutral	N	0.47338123	None	None	N
N/T	0.1629	likely_benign	0.1723	benign	-0.273	Destabilizing	0.521	D	0.343	neutral	D	0.524330126	None	None	N
N/V	0.408	ambiguous	0.4247	ambiguous	-0.089	Destabilizing	0.59	D	0.571	neutral	None	None	None	None	N
N/W	0.7046	likely_pathogenic	0.7266	pathogenic	-0.496	Destabilizing	0.996	D	0.667	neutral	None	None	None	None	N
N/Y	0.1597	likely_benign	0.1669	benign	-0.294	Destabilizing	0.979	D	0.582	neutral	N	0.513670415	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.