TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30757	92494;92495;92496	chr2:178549357;178549356;178549355	chr2:179414084;179414083;179414082
N2AB	29116	87571;87572;87573	chr2:178549357;178549356;178549355	chr2:179414084;179414083;179414082
N2A	28189	84790;84791;84792	chr2:178549357;178549356;178549355	chr2:179414084;179414083;179414082
N2B	21692	65299;65300;65301	chr2:178549357;178549356;178549355	chr2:179414084;179414083;179414082
Novex-1	21817	65674;65675;65676	chr2:178549357;178549356;178549355	chr2:179414084;179414083;179414082
Novex-2	21884	65875;65876;65877	chr2:178549357;178549356;178549355	chr2:179414084;179414083;179414082
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-112
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1208
• 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
E/Q	None	None	1.0	N	0.732	0.398	0.359357374593	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
E/A	0.574	likely_pathogenic	0.5523	ambiguous	-1.345	Destabilizing	0.999	D	0.699	prob.neutral	D	0.537001856	None	None	N
E/C	0.9516	likely_pathogenic	0.9425	pathogenic	-0.84	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/D	0.7496	likely_pathogenic	0.7032	pathogenic	-2.005	Highly Destabilizing	0.999	D	0.66	neutral	N	0.48969053	None	None	N
E/F	0.951	likely_pathogenic	0.9374	pathogenic	-0.996	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/G	0.7178	likely_pathogenic	0.662	pathogenic	-1.716	Destabilizing	1.0	D	0.773	deleterious	D	0.532028333	None	None	N
E/H	0.8481	likely_pathogenic	0.815	pathogenic	-1.016	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/I	0.8555	likely_pathogenic	0.8259	pathogenic	-0.277	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/K	0.7146	likely_pathogenic	0.6498	pathogenic	-1.718	Destabilizing	0.999	D	0.696	prob.neutral	N	0.506273848	None	None	N
E/L	0.8013	likely_pathogenic	0.7745	pathogenic	-0.277	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/M	0.8121	likely_pathogenic	0.7907	pathogenic	0.369	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/N	0.8604	likely_pathogenic	0.8202	pathogenic	-1.989	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/P	0.9983	likely_pathogenic	0.9981	pathogenic	-0.62	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/Q	0.2446	likely_benign	0.2199	benign	-1.651	Destabilizing	1.0	D	0.732	prob.delet.	N	0.481902169	None	None	N
E/R	0.7779	likely_pathogenic	0.7273	pathogenic	-1.578	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/S	0.6271	likely_pathogenic	0.5962	pathogenic	-2.518	Highly Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
E/T	0.7392	likely_pathogenic	0.7101	pathogenic	-2.17	Highly Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
E/V	0.6565	likely_pathogenic	0.6278	pathogenic	-0.62	Destabilizing	1.0	D	0.777	deleterious	D	0.549283214	None	None	N
E/W	0.9782	likely_pathogenic	0.971	pathogenic	-1.209	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/Y	0.9192	likely_pathogenic	0.9021	pathogenic	-0.912	Destabilizing	1.0	D	0.788	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.