TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24436	73531;73532;73533	chr2:178572826;178572825;178572824	chr2:179437553;179437552;179437551
N2AB	22795	68608;68609;68610	chr2:178572826;178572825;178572824	chr2:179437553;179437552;179437551
N2A	21868	65827;65828;65829	chr2:178572826;178572825;178572824	chr2:179437553;179437552;179437551
N2B	15371	46336;46337;46338	chr2:178572826;178572825;178572824	chr2:179437553;179437552;179437551
Novex-1	15496	46711;46712;46713	chr2:178572826;178572825;178572824	chr2:179437553;179437552;179437551
Novex-2	15563	46912;46913;46914	chr2:178572826;178572825;178572824	chr2:179437553;179437552;179437551
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-132
• Domain position: 6
• Structural Position: 9
• Q(SASA): 0.6873
• Predicted PPI site: I

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/E	None	None	0.805	D	0.622	0.254	0.343101102393	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
K/N	rs1708726182	None	0.935	D	0.622	0.297	0.235038932564	gnomAD-4.0.0	1.3687E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.7992E-06	0	0
K/Q	rs1301799099	None	0.983	N	0.662	0.35	0.229924730088	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/Q	rs1301799099	None	0.983	N	0.662	0.35	0.229924730088	gnomAD-4.0.0	6.57583E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47106E-05	0	0
K/R	None	None	0.944	N	0.621	0.295	0.313818047136	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.905	likely_pathogenic	0.9188	pathogenic	0.035	Stabilizing	0.916	D	0.635	neutral	None	None	None	None	I
K/C	0.961	likely_pathogenic	0.9656	pathogenic	-0.165	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	I
K/D	0.9275	likely_pathogenic	0.9355	pathogenic	0.083	Stabilizing	0.033	N	0.411	neutral	None	None	None	None	I
K/E	0.7983	likely_pathogenic	0.8113	pathogenic	0.094	Stabilizing	0.805	D	0.622	neutral	D	0.527378792	None	None	I
K/F	0.9934	likely_pathogenic	0.9945	pathogenic	-0.145	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
K/G	0.8879	likely_pathogenic	0.8996	pathogenic	-0.171	Destabilizing	0.916	D	0.567	neutral	None	None	None	None	I
K/H	0.701	likely_pathogenic	0.7333	pathogenic	-0.433	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	I
K/I	0.9652	likely_pathogenic	0.9697	pathogenic	0.499	Stabilizing	0.983	D	0.705	prob.neutral	N	0.515037985	None	None	I
K/L	0.9122	likely_pathogenic	0.9206	pathogenic	0.499	Stabilizing	0.987	D	0.609	neutral	None	None	None	None	I
K/M	0.8592	likely_pathogenic	0.8696	pathogenic	0.247	Stabilizing	0.999	D	0.659	neutral	None	None	None	None	I
K/N	0.8777	likely_pathogenic	0.8953	pathogenic	0.231	Stabilizing	0.935	D	0.622	neutral	D	0.5285923	None	None	I
K/P	0.979	likely_pathogenic	0.9781	pathogenic	0.373	Stabilizing	0.987	D	0.653	neutral	None	None	None	None	I
K/Q	0.4713	ambiguous	0.5042	ambiguous	0.077	Stabilizing	0.983	D	0.662	neutral	N	0.484262733	None	None	I
K/R	0.1127	likely_benign	0.1186	benign	-0.055	Destabilizing	0.944	D	0.621	neutral	N	0.487764398	None	None	I
K/S	0.9066	likely_pathogenic	0.9198	pathogenic	-0.244	Destabilizing	0.916	D	0.641	neutral	None	None	None	None	I
K/T	0.7871	likely_pathogenic	0.806	pathogenic	-0.084	Destabilizing	0.967	D	0.609	neutral	N	0.495919772	None	None	I
K/V	0.9391	likely_pathogenic	0.9452	pathogenic	0.373	Stabilizing	0.987	D	0.661	neutral	None	None	None	None	I
K/W	0.982	likely_pathogenic	0.9833	pathogenic	-0.176	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	I
K/Y	0.965	likely_pathogenic	0.9695	pathogenic	0.176	Stabilizing	0.996	D	0.668	neutral	None	None	None	None	I

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.