TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32308	97147;97148;97149	chr2:178542932;178542931;178542930	chr2:179407659;179407658;179407657
N2AB	30667	92224;92225;92226	chr2:178542932;178542931;178542930	chr2:179407659;179407658;179407657
N2A	29740	89443;89444;89445	chr2:178542932;178542931;178542930	chr2:179407659;179407658;179407657
N2B	23243	69952;69953;69954	chr2:178542932;178542931;178542930	chr2:179407659;179407658;179407657
Novex-1	23368	70327;70328;70329	chr2:178542932;178542931;178542930	chr2:179407659;179407658;179407657
Novex-2	23435	70528;70529;70530	chr2:178542932;178542931;178542930	chr2:179407659;179407658;179407657
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-154
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.3083
• 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	None	None	0.007	N	0.357	0.076	0.435915822735	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
L/R	rs749636019	-0.683	0.879	N	0.728	0.477	0.838891562718	gnomAD-2.1.1	4.11E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.07E-06	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	0.547	ambiguous	0.576	pathogenic	-1.569	Destabilizing	0.575	D	0.554	neutral	None	None	None	None	N
L/C	0.6867	likely_pathogenic	0.6771	pathogenic	-0.818	Destabilizing	0.991	D	0.667	neutral	None	None	None	None	N
L/D	0.9112	likely_pathogenic	0.9221	pathogenic	-1.16	Destabilizing	0.906	D	0.749	deleterious	None	None	None	None	N
L/E	0.7919	likely_pathogenic	0.8266	pathogenic	-1.172	Destabilizing	0.906	D	0.743	deleterious	None	None	None	None	N
L/F	0.1988	likely_benign	0.1858	benign	-1.19	Destabilizing	0.007	N	0.357	neutral	N	0.472125729	None	None	N
L/G	0.7489	likely_pathogenic	0.7643	pathogenic	-1.882	Destabilizing	0.906	D	0.737	prob.delet.	None	None	None	None	N
L/H	0.5568	ambiguous	0.5855	pathogenic	-1.21	Destabilizing	0.988	D	0.755	deleterious	N	0.488899242	None	None	N
L/I	0.124	likely_benign	0.1279	benign	-0.789	Destabilizing	0.003	N	0.286	neutral	N	0.483068983	None	None	N
L/K	0.5983	likely_pathogenic	0.6663	pathogenic	-1.12	Destabilizing	0.906	D	0.721	prob.delet.	None	None	None	None	N
L/M	0.1368	likely_benign	0.1538	benign	-0.536	Destabilizing	0.826	D	0.591	neutral	None	None	None	None	N
L/N	0.7276	likely_pathogenic	0.766	pathogenic	-0.842	Destabilizing	0.967	D	0.748	deleterious	None	None	None	None	N
L/P	0.5892	likely_pathogenic	0.6046	pathogenic	-1.018	Destabilizing	0.957	D	0.749	deleterious	N	0.488899242	None	None	N
L/Q	0.495	ambiguous	0.553	ambiguous	-1.024	Destabilizing	0.967	D	0.724	prob.delet.	None	None	None	None	N
L/R	0.4899	ambiguous	0.5407	ambiguous	-0.529	Destabilizing	0.879	D	0.728	prob.delet.	N	0.488645752	None	None	N
L/S	0.6731	likely_pathogenic	0.7045	pathogenic	-1.378	Destabilizing	0.906	D	0.708	prob.delet.	None	None	None	None	N
L/T	0.3307	likely_benign	0.363	ambiguous	-1.273	Destabilizing	0.826	D	0.625	neutral	None	None	None	None	N
L/V	0.135	likely_benign	0.1391	benign	-1.018	Destabilizing	0.013	N	0.371	neutral	N	0.485096899	None	None	N
L/W	0.4415	ambiguous	0.4271	ambiguous	-1.279	Destabilizing	0.991	D	0.744	deleterious	None	None	None	None	N
L/Y	0.5796	likely_pathogenic	0.5828	pathogenic	-1.065	Destabilizing	0.704	D	0.675	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.