TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22663	68212;68213;68214	chr2:178579043;178579042;178579041	chr2:179443770;179443769;179443768
N2AB	21022	63289;63290;63291	chr2:178579043;178579042;178579041	chr2:179443770;179443769;179443768
N2A	20095	60508;60509;60510	chr2:178579043;178579042;178579041	chr2:179443770;179443769;179443768
N2B	13598	41017;41018;41019	chr2:178579043;178579042;178579041	chr2:179443770;179443769;179443768
Novex-1	13723	41392;41393;41394	chr2:178579043;178579042;178579041	chr2:179443770;179443769;179443768
Novex-2	13790	41593;41594;41595	chr2:178579043;178579042;178579041	chr2:179443770;179443769;179443768
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-52
• Domain position: 21
• Structural Position: 22
• Q(SASA): 0.0919
• 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	rs1485610846	-1.54	0.999	N	0.734	0.4	0.529311486226	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
L/F	rs1485610846	-1.54	0.999	N	0.734	0.4	0.529311486226	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
L/F	rs1485610846	-1.54	0.999	N	0.734	0.4	0.529311486226	gnomAD-4.0.0	5.12785E-06	None	None	None	None	N	None	6.76888E-05	0	None	0	0	None	0	0	0	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	0.8726	likely_pathogenic	0.839	pathogenic	-2.683	Highly Destabilizing	0.994	D	0.708	prob.delet.	None	None	None	None	N
L/C	0.7755	likely_pathogenic	0.7556	pathogenic	-1.657	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9995	pathogenic	-3.36	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/E	0.9971	likely_pathogenic	0.9957	pathogenic	-3.036	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/F	0.4965	ambiguous	0.4064	ambiguous	-1.641	Destabilizing	0.999	D	0.734	prob.delet.	N	0.493730953	None	None	N
L/G	0.9852	likely_pathogenic	0.9798	pathogenic	-3.264	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
L/H	0.9925	likely_pathogenic	0.9886	pathogenic	-3.082	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/I	0.1171	likely_benign	0.1046	benign	-0.911	Destabilizing	0.962	D	0.573	neutral	N	0.483259868	None	None	N
L/K	0.9964	likely_pathogenic	0.9947	pathogenic	-2.065	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/M	0.1945	likely_benign	0.1733	benign	-1.1	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
L/N	0.9973	likely_pathogenic	0.9963	pathogenic	-2.864	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
L/P	0.9959	likely_pathogenic	0.9922	pathogenic	-1.497	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
L/Q	0.9859	likely_pathogenic	0.9796	pathogenic	-2.441	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/R	0.9916	likely_pathogenic	0.9872	pathogenic	-2.282	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
L/S	0.9875	likely_pathogenic	0.9808	pathogenic	-3.271	Highly Destabilizing	0.999	D	0.877	deleterious	D	0.534498593	None	None	N
L/T	0.9409	likely_pathogenic	0.9257	pathogenic	-2.785	Highly Destabilizing	0.998	D	0.794	deleterious	None	None	None	None	N
L/V	0.1098	likely_benign	0.1025	benign	-1.497	Destabilizing	0.619	D	0.348	neutral	N	0.455974479	None	None	N
L/W	0.9716	likely_pathogenic	0.9555	pathogenic	-1.961	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/Y	0.9744	likely_pathogenic	0.9597	pathogenic	-1.839	Destabilizing	1.0	D	0.807	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.