TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24627	74104;74105;74106	chr2:178572253;178572252;178572251	chr2:179436980;179436979;179436978
N2AB	22986	69181;69182;69183	chr2:178572253;178572252;178572251	chr2:179436980;179436979;179436978
N2A	22059	66400;66401;66402	chr2:178572253;178572252;178572251	chr2:179436980;179436979;179436978
N2B	15562	46909;46910;46911	chr2:178572253;178572252;178572251	chr2:179436980;179436979;179436978
Novex-1	15687	47284;47285;47286	chr2:178572253;178572252;178572251	chr2:179436980;179436979;179436978
Novex-2	15754	47485;47486;47487	chr2:178572253;178572252;178572251	chr2:179436980;179436979;179436978
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: Fn3-67
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.4182
• 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/G	None	None	0.93	N	0.59	0.454	0.298056030225	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
D/A	0.7605	likely_pathogenic	0.6857	pathogenic	-0.546	Destabilizing	0.901	D	0.585	neutral	N	0.472672231	None	None	N
D/C	0.9817	likely_pathogenic	0.9757	pathogenic	-0.087	Destabilizing	0.996	D	0.72	prob.delet.	None	None	None	None	N
D/E	0.6534	likely_pathogenic	0.5677	pathogenic	-0.499	Destabilizing	0.006	N	0.097	neutral	N	0.467473978	None	None	N
D/F	0.9774	likely_pathogenic	0.9676	pathogenic	-0.306	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
D/G	0.7156	likely_pathogenic	0.6123	pathogenic	-0.827	Destabilizing	0.93	D	0.59	neutral	N	0.484548742	None	None	N
D/H	0.8982	likely_pathogenic	0.8679	pathogenic	-0.461	Destabilizing	0.996	D	0.603	neutral	N	0.492830855	None	None	N
D/I	0.9646	likely_pathogenic	0.9513	pathogenic	0.174	Stabilizing	0.999	D	0.659	neutral	None	None	None	None	N
D/K	0.9523	likely_pathogenic	0.9405	pathogenic	0.035	Stabilizing	0.366	N	0.271	neutral	None	None	None	None	N
D/L	0.9343	likely_pathogenic	0.9136	pathogenic	0.174	Stabilizing	0.997	D	0.585	neutral	None	None	None	None	N
D/M	0.9759	likely_pathogenic	0.9676	pathogenic	0.515	Stabilizing	0.999	D	0.655	neutral	None	None	None	None	N
D/N	0.4477	ambiguous	0.3587	ambiguous	-0.399	Destabilizing	0.891	D	0.594	neutral	N	0.502375986	None	None	N
D/P	0.9964	likely_pathogenic	0.9952	pathogenic	-0.042	Destabilizing	0.949	D	0.553	neutral	None	None	None	None	N
D/Q	0.9265	likely_pathogenic	0.907	pathogenic	-0.32	Destabilizing	0.942	D	0.531	neutral	None	None	None	None	N
D/R	0.9547	likely_pathogenic	0.9442	pathogenic	0.158	Stabilizing	0.987	D	0.53	neutral	None	None	None	None	N
D/S	0.6693	likely_pathogenic	0.5695	pathogenic	-0.559	Destabilizing	0.923	D	0.569	neutral	None	None	None	None	N
D/T	0.8767	likely_pathogenic	0.8276	pathogenic	-0.328	Destabilizing	0.916	D	0.581	neutral	None	None	None	None	N
D/V	0.8716	likely_pathogenic	0.8359	pathogenic	-0.042	Destabilizing	0.976	D	0.587	neutral	N	0.504565555	None	None	N
D/W	0.9942	likely_pathogenic	0.9926	pathogenic	-0.103	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
D/Y	0.85	likely_pathogenic	0.8049	pathogenic	-0.051	Destabilizing	0.999	D	0.665	neutral	N	0.505833002	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.