TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8609	26050;26051;26052	chr2:178715589;178715588;178715587	chr2:179580316;179580315;179580314
N2AB	8292	25099;25100;25101	chr2:178715589;178715588;178715587	chr2:179580316;179580315;179580314
N2A	7365	22318;22319;22320	chr2:178715589;178715588;178715587	chr2:179580316;179580315;179580314
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-71
• Domain position: 61
• Structural Position: 140
• Q(SASA): 0.0553
• 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
M/I	rs1407524421	None	None	N	0.279	0.222	0.221019684889	gnomAD-4.0.0	2.05282E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69863E-06	0	0
M/V	rs1369418506	None	None	N	0.273	0.11	0.377274123778	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.9305E-04	None	0	0	0	0	0
M/V	rs1369418506	None	None	N	0.273	0.11	0.377274123778	gnomAD-4.0.0	6.57445E-06	None	None	None	None	N	None	0	0	None	0	1.9305E-04	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
M/A	0.8047	likely_pathogenic	0.805	pathogenic	-1.636	Destabilizing	None	N	0.442	neutral	None	None	None	None	N
M/C	0.9211	likely_pathogenic	0.927	pathogenic	-2.576	Highly Destabilizing	0.936	D	0.751	deleterious	None	None	None	None	N
M/D	0.9935	likely_pathogenic	0.9941	pathogenic	-2.109	Highly Destabilizing	0.937	D	0.762	deleterious	None	None	None	None	N
M/E	0.9617	likely_pathogenic	0.9641	pathogenic	-1.853	Destabilizing	0.748	D	0.716	prob.delet.	None	None	None	None	N
M/F	0.5181	ambiguous	0.4998	ambiguous	-0.291	Destabilizing	0.036	N	0.574	neutral	None	None	None	None	N
M/G	0.929	likely_pathogenic	0.9336	pathogenic	-2.084	Highly Destabilizing	0.141	N	0.701	prob.neutral	None	None	None	None	N
M/H	0.9553	likely_pathogenic	0.952	pathogenic	-1.977	Destabilizing	0.995	D	0.815	deleterious	None	None	None	None	N
M/I	0.3643	ambiguous	0.3724	ambiguous	-0.32	Destabilizing	None	N	0.279	neutral	N	0.309008042	None	None	N
M/K	0.8557	likely_pathogenic	0.8549	pathogenic	-1.191	Destabilizing	0.774	D	0.621	neutral	N	0.49224015	None	None	N
M/L	0.1976	likely_benign	0.1991	benign	-0.32	Destabilizing	None	N	0.263	neutral	N	0.392238006	None	None	N
M/N	0.9411	likely_pathogenic	0.9395	pathogenic	-1.757	Destabilizing	0.981	D	0.775	deleterious	None	None	None	None	N
M/P	0.9951	likely_pathogenic	0.9951	pathogenic	-0.747	Destabilizing	0.937	D	0.747	deleterious	None	None	None	None	N
M/Q	0.8485	likely_pathogenic	0.8458	pathogenic	-1.351	Destabilizing	0.954	D	0.654	neutral	None	None	None	None	N
M/R	0.8766	likely_pathogenic	0.8753	pathogenic	-1.551	Destabilizing	0.937	D	0.677	prob.neutral	N	0.49224015	None	None	N
M/S	0.8975	likely_pathogenic	0.8962	pathogenic	-2.097	Highly Destabilizing	0.835	D	0.609	neutral	None	None	None	None	N
M/T	0.7925	likely_pathogenic	0.785	pathogenic	-1.721	Destabilizing	0.696	D	0.567	neutral	N	0.491733171	None	None	N
M/V	0.2005	likely_benign	0.1926	benign	-0.747	Destabilizing	None	N	0.273	neutral	N	0.415922942	None	None	N
M/W	0.9334	likely_pathogenic	0.9351	pathogenic	-0.693	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
M/Y	0.8892	likely_pathogenic	0.887	pathogenic	-0.636	Destabilizing	0.965	D	0.71	prob.delet.	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.