TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7924	23995;23996;23997	chr2:178719722;178719721;178719720	chr2:179584449;179584448;179584447
N2AB	7607	23044;23045;23046	chr2:178719722;178719721;178719720	chr2:179584449;179584448;179584447
N2A	6680	20263;20264;20265	chr2:178719722;178719721;178719720	chr2:179584449;179584448;179584447
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-64
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1682
• 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	rs373894127	-1.121	0.999	D	0.725	0.412	0.277730125212	gnomAD-2.1.1	2.41E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	5.34E-05	0
K/N	rs373894127	-1.121	0.999	D	0.725	0.412	0.277730125212	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	2.94E-05	0	0
K/N	rs373894127	-1.121	0.999	D	0.725	0.412	0.277730125212	gnomAD-4.0.0	1.42537E-05	None	None	None	None	N	None	0	1.66706E-05	None	0	0	None	0	0	1.86487E-05	0	0
K/Q	rs770650362	-1.018	0.999	D	0.709	0.409	0.375147631797	gnomAD-2.1.1	7.14E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.56E-05	0
K/Q	rs770650362	-1.018	0.999	D	0.709	0.409	0.375147631797	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
K/Q	rs770650362	-1.018	0.999	D	0.709	0.409	0.375147631797	gnomAD-4.0.0	6.81684E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.32425E-06	0	0
K/R	rs749465424	-0.743	0.64	N	0.355	0.28	0.228597637076	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	5.79E-05	None	0	0	None	0	None	0	0	0
K/R	rs749465424	-0.743	0.64	N	0.355	0.28	0.228597637076	gnomAD-4.0.0	3.18287E-06	None	None	None	None	N	None	0	4.57289E-05	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
K/A	0.9666	likely_pathogenic	0.963	pathogenic	-1.091	Destabilizing	0.998	D	0.578	neutral	None	None	None	None	N
K/C	0.9429	likely_pathogenic	0.9438	pathogenic	-1.102	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
K/D	0.996	likely_pathogenic	0.9962	pathogenic	-0.773	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/E	0.9046	likely_pathogenic	0.8992	pathogenic	-0.592	Destabilizing	0.996	D	0.526	neutral	D	0.529614661	None	None	N
K/F	0.9704	likely_pathogenic	0.9682	pathogenic	-0.707	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
K/G	0.9865	likely_pathogenic	0.9862	pathogenic	-1.521	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/H	0.7097	likely_pathogenic	0.7238	pathogenic	-1.863	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
K/I	0.8668	likely_pathogenic	0.8563	pathogenic	0.069	Stabilizing	1.0	D	0.873	deleterious	D	0.533120153	None	None	N
K/L	0.8422	likely_pathogenic	0.8247	pathogenic	0.069	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/M	0.7725	likely_pathogenic	0.7559	pathogenic	0.051	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/N	0.9815	likely_pathogenic	0.9811	pathogenic	-1.115	Destabilizing	0.999	D	0.725	prob.delet.	D	0.529361172	None	None	N
K/P	0.9978	likely_pathogenic	0.9976	pathogenic	-0.29	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
K/Q	0.5803	likely_pathogenic	0.5696	pathogenic	-1.07	Destabilizing	0.999	D	0.709	prob.delet.	D	0.528854193	None	None	N
K/R	0.1057	likely_benign	0.1085	benign	-0.939	Destabilizing	0.64	D	0.355	neutral	N	0.472282794	None	None	N
K/S	0.9793	likely_pathogenic	0.9772	pathogenic	-1.817	Destabilizing	0.998	D	0.593	neutral	None	None	None	None	N
K/T	0.946	likely_pathogenic	0.9388	pathogenic	-1.392	Destabilizing	0.999	D	0.76	deleterious	D	0.529107682	None	None	N
K/V	0.8524	likely_pathogenic	0.8411	pathogenic	-0.29	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
K/W	0.9454	likely_pathogenic	0.9417	pathogenic	-0.587	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
K/Y	0.919	likely_pathogenic	0.9192	pathogenic	-0.272	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.