TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28004	84235;84236;84237	chr2:178562122;178562121;178562120	chr2:179426849;179426848;179426847
N2AB	26363	79312;79313;79314	chr2:178562122;178562121;178562120	chr2:179426849;179426848;179426847
N2A	25436	76531;76532;76533	chr2:178562122;178562121;178562120	chr2:179426849;179426848;179426847
N2B	18939	57040;57041;57042	chr2:178562122;178562121;178562120	chr2:179426849;179426848;179426847
Novex-1	19064	57415;57416;57417	chr2:178562122;178562121;178562120	chr2:179426849;179426848;179426847
Novex-2	19131	57616;57617;57618	chr2:178562122;178562121;178562120	chr2:179426849;179426848;179426847
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-142
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.4802
• 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
K/R	rs776987640	0.204	0.001	D	0.253	0.084	0.255777322467	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.99E-06	0
K/R	rs776987640	0.204	0.001	D	0.253	0.084	0.255777322467	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs776987640	0.204	0.001	D	0.253	0.084	0.255777322467	gnomAD-4.0.0	6.57056E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46985E-05	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
K/A	0.5135	ambiguous	0.5038	ambiguous	0.042	Stabilizing	0.157	N	0.533	neutral	None	None	None	None	N
K/C	0.7372	likely_pathogenic	0.7344	pathogenic	-0.445	Destabilizing	0.968	D	0.645	neutral	None	None	None	None	N
K/D	0.8481	likely_pathogenic	0.8249	pathogenic	-0.276	Destabilizing	0.567	D	0.466	neutral	None	None	None	None	N
K/E	0.3399	likely_benign	0.3362	benign	-0.28	Destabilizing	0.124	N	0.529	neutral	N	0.48308589	None	None	N
K/F	0.8766	likely_pathogenic	0.8492	pathogenic	-0.277	Destabilizing	0.726	D	0.617	neutral	None	None	None	None	N
K/G	0.6359	likely_pathogenic	0.6015	pathogenic	-0.098	Destabilizing	0.272	N	0.483	neutral	None	None	None	None	N
K/H	0.386	ambiguous	0.3724	ambiguous	-0.208	Destabilizing	0.909	D	0.51	neutral	None	None	None	None	N
K/I	0.4876	ambiguous	0.4832	ambiguous	0.329	Stabilizing	0.497	N	0.611	neutral	N	0.512118831	None	None	N
K/L	0.4578	ambiguous	0.4531	ambiguous	0.329	Stabilizing	0.157	N	0.501	neutral	None	None	None	None	N
K/M	0.3653	ambiguous	0.3676	ambiguous	-0.099	Destabilizing	0.968	D	0.513	neutral	None	None	None	None	N
K/N	0.7097	likely_pathogenic	0.6927	pathogenic	-0.016	Destabilizing	0.497	N	0.442	neutral	N	0.4949984	None	None	N
K/P	0.7549	likely_pathogenic	0.7455	pathogenic	0.258	Stabilizing	0.726	D	0.499	neutral	None	None	None	None	N
K/Q	0.1754	likely_benign	0.1742	benign	-0.133	Destabilizing	0.497	N	0.475	neutral	N	0.49396167	None	None	N
K/R	0.0694	likely_benign	0.0681	benign	-0.117	Destabilizing	0.001	N	0.253	neutral	D	0.533808906	None	None	N
K/S	0.6512	likely_pathogenic	0.6374	pathogenic	-0.361	Destabilizing	0.157	N	0.491	neutral	None	None	None	None	N
K/T	0.3104	likely_benign	0.3251	benign	-0.243	Destabilizing	0.002	N	0.299	neutral	D	0.532539469	None	None	N
K/V	0.4403	ambiguous	0.4393	ambiguous	0.258	Stabilizing	0.396	N	0.457	neutral	None	None	None	None	N
K/W	0.7844	likely_pathogenic	0.7331	pathogenic	-0.396	Destabilizing	0.968	D	0.669	neutral	None	None	None	None	N
K/Y	0.7619	likely_pathogenic	0.7281	pathogenic	-0.038	Destabilizing	0.726	D	0.571	neutral	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.