TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17268	52027;52028;52029	chr2:178609508;178609507;178609506	chr2:179474235;179474234;179474233
N2AB	15627	47104;47105;47106	chr2:178609508;178609507;178609506	chr2:179474235;179474234;179474233
N2A	14700	44323;44324;44325	chr2:178609508;178609507;178609506	chr2:179474235;179474234;179474233
N2B	8203	24832;24833;24834	chr2:178609508;178609507;178609506	chr2:179474235;179474234;179474233
Novex-1	8328	25207;25208;25209	chr2:178609508;178609507;178609506	chr2:179474235;179474234;179474233
Novex-2	8395	25408;25409;25410	chr2:178609508;178609507;178609506	chr2:179474235;179474234;179474233
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-112
• Domain position: 18
• Structural Position: 31
• Q(SASA): 0.3526
• 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
D/A	None	None	0.565	N	0.617	0.357	0.421060224861	gnomAD-4.0.0	4.10815E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39949E-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
D/A	0.2094	likely_benign	0.2094	benign	-0.398	Destabilizing	0.565	D	0.617	neutral	N	0.509633162	None	None	N
D/C	0.6257	likely_pathogenic	0.6196	pathogenic	-0.112	Destabilizing	0.996	D	0.768	deleterious	None	None	None	None	N
D/E	0.1707	likely_benign	0.1648	benign	-0.719	Destabilizing	0.003	N	0.221	neutral	N	0.485686885	None	None	N
D/F	0.4972	ambiguous	0.4906	ambiguous	-0.095	Destabilizing	0.987	D	0.774	deleterious	None	None	None	None	N
D/G	0.2687	likely_benign	0.2736	benign	-0.746	Destabilizing	0.722	D	0.523	neutral	N	0.500051283	None	None	N
D/H	0.23	likely_benign	0.226	benign	-0.452	Destabilizing	0.949	D	0.664	neutral	N	0.484909542	None	None	N
D/I	0.3102	likely_benign	0.3122	benign	0.515	Stabilizing	0.961	D	0.776	deleterious	None	None	None	None	N
D/K	0.3516	ambiguous	0.3381	benign	-0.158	Destabilizing	0.633	D	0.551	neutral	None	None	None	None	N
D/L	0.3321	likely_benign	0.3264	benign	0.515	Stabilizing	0.923	D	0.718	prob.delet.	None	None	None	None	N
D/M	0.5725	likely_pathogenic	0.5738	pathogenic	0.91	Stabilizing	0.996	D	0.766	deleterious	None	None	None	None	N
D/N	0.1305	likely_benign	0.1312	benign	-0.628	Destabilizing	0.722	D	0.517	neutral	N	0.513932279	None	None	N
D/P	0.7189	likely_pathogenic	0.7081	pathogenic	0.237	Stabilizing	0.961	D	0.621	neutral	None	None	None	None	N
D/Q	0.3164	likely_benign	0.303	benign	-0.486	Destabilizing	0.096	N	0.359	neutral	None	None	None	None	N
D/R	0.3919	ambiguous	0.3754	ambiguous	-0.071	Destabilizing	0.858	D	0.662	neutral	None	None	None	None	N
D/S	0.1608	likely_benign	0.1604	benign	-0.846	Destabilizing	0.633	D	0.519	neutral	None	None	None	None	N
D/T	0.2272	likely_benign	0.2311	benign	-0.555	Destabilizing	0.775	D	0.561	neutral	None	None	None	None	N
D/V	0.195	likely_benign	0.1933	benign	0.237	Stabilizing	0.901	D	0.719	prob.delet.	N	0.506681019	None	None	N
D/W	0.8173	likely_pathogenic	0.8095	pathogenic	0.051	Stabilizing	0.996	D	0.721	prob.delet.	None	None	None	None	N
D/Y	0.2053	likely_benign	0.2068	benign	0.154	Stabilizing	0.983	D	0.781	deleterious	N	0.500304772	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.