TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32636	98131;98132;98133	chr2:178540260;178540259;178540258	chr2:179404987;179404986;179404985
N2AB	30995	93208;93209;93210	chr2:178540260;178540259;178540258	chr2:179404987;179404986;179404985
N2A	30068	90427;90428;90429	chr2:178540260;178540259;178540258	chr2:179404987;179404986;179404985
N2B	23571	70936;70937;70938	chr2:178540260;178540259;178540258	chr2:179404987;179404986;179404985
Novex-1	23696	71311;71312;71313	chr2:178540260;178540259;178540258	chr2:179404987;179404986;179404985
Novex-2	23763	71512;71513;71514	chr2:178540260;178540259;178540258	chr2:179404987;179404986;179404985
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-126
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.2194
• 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	rs767660102	-1.647	0.998	N	0.769	0.182	0.539970339866	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
L/F	rs767660102	-1.647	0.998	N	0.769	0.182	0.539970339866	gnomAD-4.0.0	1.59117E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85822E-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	0.6814	likely_pathogenic	0.6848	pathogenic	-2.748	Highly Destabilizing	0.998	D	0.639	neutral	None	None	None	None	N
L/C	0.6598	likely_pathogenic	0.6417	pathogenic	-2.197	Highly Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
L/D	0.9406	likely_pathogenic	0.9398	pathogenic	-3.238	Highly Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
L/E	0.7313	likely_pathogenic	0.734	pathogenic	-3.074	Highly Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
L/F	0.2076	likely_benign	0.1779	benign	-1.657	Destabilizing	0.998	D	0.769	deleterious	N	0.475768175	None	None	N
L/G	0.9274	likely_pathogenic	0.9291	pathogenic	-3.222	Highly Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
L/H	0.4584	ambiguous	0.4352	ambiguous	-2.529	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/I	0.1025	likely_benign	0.1034	benign	-1.392	Destabilizing	0.998	D	0.542	neutral	None	None	None	None	N
L/K	0.6873	likely_pathogenic	0.7004	pathogenic	-2.189	Highly Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
L/M	0.1472	likely_benign	0.1397	benign	-1.406	Destabilizing	1.0	D	0.795	deleterious	N	0.475480173	None	None	N
L/N	0.7234	likely_pathogenic	0.6915	pathogenic	-2.419	Highly Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
L/P	0.9913	likely_pathogenic	0.9939	pathogenic	-1.825	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
L/Q	0.4003	ambiguous	0.3956	ambiguous	-2.394	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/R	0.5595	ambiguous	0.5831	pathogenic	-1.717	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
L/S	0.7044	likely_pathogenic	0.6892	pathogenic	-3.055	Highly Destabilizing	0.999	D	0.726	prob.delet.	N	0.482576717	None	None	N
L/T	0.4918	ambiguous	0.4805	ambiguous	-2.767	Highly Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
L/V	0.1337	likely_benign	0.1396	benign	-1.825	Destabilizing	0.998	D	0.58	neutral	N	0.392824291	None	None	N
L/W	0.4195	ambiguous	0.4141	ambiguous	-1.994	Destabilizing	1.0	D	0.789	deleterious	N	0.51372913	None	None	N
L/Y	0.448	ambiguous	0.3934	ambiguous	-1.8	Destabilizing	0.91	D	0.418	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.