TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27779	83560;83561;83562	chr2:178562797;178562796;178562795	chr2:179427524;179427523;179427522
N2AB	26138	78637;78638;78639	chr2:178562797;178562796;178562795	chr2:179427524;179427523;179427522
N2A	25211	75856;75857;75858	chr2:178562797;178562796;178562795	chr2:179427524;179427523;179427522
N2B	18714	56365;56366;56367	chr2:178562797;178562796;178562795	chr2:179427524;179427523;179427522
Novex-1	18839	56740;56741;56742	chr2:178562797;178562796;178562795	chr2:179427524;179427523;179427522
Novex-2	18906	56941;56942;56943	chr2:178562797;178562796;178562795	chr2:179427524;179427523;179427522
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-90
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.5795
• 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
K/N	rs1410411613	0.063	0.864	N	0.478	0.145	0.201204373187	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
K/N	rs1410411613	0.063	0.864	N	0.478	0.145	0.201204373187	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs1410411613	0.063	0.864	N	0.478	0.145	0.201204373187	gnomAD-4.0.0	2.56416E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78833E-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
K/A	0.4052	ambiguous	0.4265	ambiguous	-0.348	Destabilizing	0.707	D	0.447	neutral	None	None	None	None	N
K/C	0.5901	likely_pathogenic	0.5854	pathogenic	-0.502	Destabilizing	0.995	D	0.657	neutral	None	None	None	None	N
K/D	0.6739	likely_pathogenic	0.7097	pathogenic	-0.191	Destabilizing	0.894	D	0.463	neutral	None	None	None	None	N
K/E	0.2639	likely_benign	0.2975	benign	-0.119	Destabilizing	0.477	N	0.513	neutral	N	0.479307125	None	None	N
K/F	0.8175	likely_pathogenic	0.8429	pathogenic	-0.19	Destabilizing	0.945	D	0.644	neutral	None	None	None	None	N
K/G	0.3762	ambiguous	0.3767	ambiguous	-0.677	Destabilizing	0.707	D	0.459	neutral	None	None	None	None	N
K/H	0.3189	likely_benign	0.3294	benign	-1.039	Destabilizing	0.985	D	0.491	neutral	None	None	None	None	N
K/I	0.6037	likely_pathogenic	0.6346	pathogenic	0.482	Stabilizing	0.894	D	0.643	neutral	None	None	None	None	N
K/L	0.4273	ambiguous	0.4613	ambiguous	0.482	Stabilizing	0.707	D	0.461	neutral	None	None	None	None	N
K/M	0.2957	likely_benign	0.3195	benign	0.419	Stabilizing	0.993	D	0.488	neutral	D	0.522271255	None	None	N
K/N	0.4815	ambiguous	0.5178	ambiguous	-0.261	Destabilizing	0.864	D	0.478	neutral	N	0.44694399	None	None	N
K/P	0.9249	likely_pathogenic	0.9328	pathogenic	0.236	Stabilizing	0.945	D	0.514	neutral	None	None	None	None	N
K/Q	0.1332	likely_benign	0.1395	benign	-0.451	Destabilizing	0.864	D	0.525	neutral	N	0.475093384	None	None	N
K/R	0.0747	likely_benign	0.0769	benign	-0.425	Destabilizing	0.013	N	0.279	neutral	N	0.422299049	None	None	N
K/S	0.4134	ambiguous	0.4448	ambiguous	-0.887	Destabilizing	0.547	D	0.488	neutral	None	None	None	None	N
K/T	0.164	likely_benign	0.1735	benign	-0.628	Destabilizing	0.053	N	0.303	neutral	N	0.351318811	None	None	N
K/V	0.4903	ambiguous	0.5237	ambiguous	0.236	Stabilizing	0.894	D	0.453	neutral	None	None	None	None	N
K/W	0.7911	likely_pathogenic	0.8021	pathogenic	-0.06	Destabilizing	0.995	D	0.67	neutral	None	None	None	None	N
K/Y	0.7114	likely_pathogenic	0.7358	pathogenic	0.258	Stabilizing	0.945	D	0.608	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.