TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24635	74128;74129;74130	chr2:178572229;178572228;178572227	chr2:179436956;179436955;179436954
N2AB	22994	69205;69206;69207	chr2:178572229;178572228;178572227	chr2:179436956;179436955;179436954
N2A	22067	66424;66425;66426	chr2:178572229;178572228;178572227	chr2:179436956;179436955;179436954
N2B	15570	46933;46934;46935	chr2:178572229;178572228;178572227	chr2:179436956;179436955;179436954
Novex-1	15695	47308;47309;47310	chr2:178572229;178572228;178572227	chr2:179436956;179436955;179436954
Novex-2	15762	47509;47510;47511	chr2:178572229;178572228;178572227	chr2:179436956;179436955;179436954
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-67
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1273
• 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/V	rs757091463	-1.204	0.998	N	0.571	0.335	0.461144880706	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
L/V	rs757091463	-1.204	0.998	N	0.571	0.335	0.461144880706	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
L/V	rs757091463	-1.204	0.998	N	0.571	0.335	0.461144880706	gnomAD-4.0.0	2.56348E-06	None	None	None	None	N	None	0	1.69555E-05	None	0	0	None	0	0	2.39396E-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	0.9752	likely_pathogenic	0.9754	pathogenic	-2.564	Highly Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
L/C	0.9567	likely_pathogenic	0.9579	pathogenic	-1.885	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9998	pathogenic	-3.172	Highly Destabilizing	1.0	D	0.945	deleterious	None	None	None	None	N
L/E	0.9991	likely_pathogenic	0.999	pathogenic	-2.827	Highly Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
L/F	0.6282	likely_pathogenic	0.5495	ambiguous	-1.546	Destabilizing	1.0	D	0.739	prob.delet.	N	0.51637743	None	None	N
L/G	0.9974	likely_pathogenic	0.9974	pathogenic	-3.209	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
L/H	0.9967	likely_pathogenic	0.9962	pathogenic	-3.078	Highly Destabilizing	1.0	D	0.913	deleterious	D	0.558968723	None	None	N
L/I	0.1538	likely_benign	0.1555	benign	-0.624	Destabilizing	0.997	D	0.549	neutral	D	0.527760007	None	None	N
L/K	0.998	likely_pathogenic	0.9978	pathogenic	-1.912	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
L/M	0.4167	ambiguous	0.4016	ambiguous	-0.882	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
L/N	0.999	likely_pathogenic	0.9989	pathogenic	-2.662	Highly Destabilizing	1.0	D	0.948	deleterious	None	None	None	None	N
L/P	0.9987	likely_pathogenic	0.9986	pathogenic	-1.262	Destabilizing	1.0	D	0.949	deleterious	D	0.558968723	None	None	N
L/Q	0.9965	likely_pathogenic	0.9961	pathogenic	-2.234	Highly Destabilizing	1.0	D	0.944	deleterious	None	None	None	None	N
L/R	0.9954	likely_pathogenic	0.9949	pathogenic	-2.144	Highly Destabilizing	1.0	D	0.929	deleterious	D	0.558968723	None	None	N
L/S	0.9979	likely_pathogenic	0.9977	pathogenic	-3.243	Highly Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
L/T	0.9888	likely_pathogenic	0.9885	pathogenic	-2.715	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/V	0.2533	likely_benign	0.2584	benign	-1.262	Destabilizing	0.998	D	0.571	neutral	N	0.473182891	None	None	N
L/W	0.9849	likely_pathogenic	0.9796	pathogenic	-1.948	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/Y	0.9834	likely_pathogenic	0.9793	pathogenic	-1.711	Destabilizing	1.0	D	0.849	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.