TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14592	43999;44000;44001	chr2:178631274;178631273;178631272	chr2:179496001;179496000;179495999
N2AB	12951	39076;39077;39078	chr2:178631274;178631273;178631272	chr2:179496001;179496000;179495999
N2A	12024	36295;36296;36297	chr2:178631274;178631273;178631272	chr2:179496001;179496000;179495999
N2B	5527	16804;16805;16806	chr2:178631274;178631273;178631272	chr2:179496001;179496000;179495999
Novex-1	5652	17179;17180;17181	chr2:178631274;178631273;178631272	chr2:179496001;179496000;179495999
Novex-2	5719	17380;17381;17382	chr2:178631274;178631273;178631272	chr2:179496001;179496000;179495999
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-97
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2568
• 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	rs1480406198	-1.649	1.0	D	0.72	0.383	0.476832112026	gnomAD-2.1.1	4.11E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.32E-05	None	0	0	0
L/F	rs1480406198	-1.649	1.0	D	0.72	0.383	0.476832112026	gnomAD-4.0.0	5.48673E-06	None	None	None	None	N	None	0	0	None	0	5.07151E-05	None	0	0	0	5.82289E-05	1.66014E-05

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	0.9385	likely_pathogenic	0.958	pathogenic	-1.989	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
L/C	0.9598	likely_pathogenic	0.9779	pathogenic	-1.608	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
L/D	0.9977	likely_pathogenic	0.9985	pathogenic	-1.255	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/E	0.9854	likely_pathogenic	0.9905	pathogenic	-1.187	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
L/F	0.7745	likely_pathogenic	0.8458	pathogenic	-1.399	Destabilizing	1.0	D	0.72	prob.delet.	D	0.626379875	None	None	N
L/G	0.9865	likely_pathogenic	0.9912	pathogenic	-2.377	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
L/H	0.9777	likely_pathogenic	0.9873	pathogenic	-1.571	Destabilizing	1.0	D	0.881	deleterious	D	0.651937956	None	None	N
L/I	0.2299	likely_benign	0.3073	benign	-0.955	Destabilizing	0.999	D	0.519	neutral	D	0.56142547	None	None	N
L/K	0.979	likely_pathogenic	0.9859	pathogenic	-1.222	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/M	0.4187	ambiguous	0.5104	ambiguous	-0.941	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
L/N	0.9866	likely_pathogenic	0.9907	pathogenic	-1.145	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/P	0.8805	likely_pathogenic	0.9177	pathogenic	-1.272	Destabilizing	1.0	D	0.908	deleterious	N	0.433099079	None	None	N
L/Q	0.9561	likely_pathogenic	0.9739	pathogenic	-1.259	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/R	0.963	likely_pathogenic	0.9753	pathogenic	-0.769	Destabilizing	1.0	D	0.891	deleterious	D	0.66521297	None	None	N
L/S	0.9855	likely_pathogenic	0.9922	pathogenic	-1.941	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/T	0.9418	likely_pathogenic	0.9634	pathogenic	-1.74	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/V	0.3882	ambiguous	0.4881	ambiguous	-1.272	Destabilizing	0.999	D	0.502	neutral	D	0.591145029	None	None	N
L/W	0.9511	likely_pathogenic	0.9753	pathogenic	-1.457	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
L/Y	0.9765	likely_pathogenic	0.9866	pathogenic	-1.213	Destabilizing	1.0	D	0.865	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.