TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1378	4357;4358;4359	chr2:178778950;178778949;178778948	chr2:179643677;179643676;179643675
N2AB	1378	4357;4358;4359	chr2:178778950;178778949;178778948	chr2:179643677;179643676;179643675
N2A	1378	4357;4358;4359	chr2:178778950;178778949;178778948	chr2:179643677;179643676;179643675
N2B	1332	4219;4220;4221	chr2:178778950;178778949;178778948	chr2:179643677;179643676;179643675
Novex-1	1332	4219;4220;4221	chr2:178778950;178778949;178778948	chr2:179643677;179643676;179643675
Novex-2	1332	4219;4220;4221	chr2:178778950;178778949;178778948	chr2:179643677;179643676;179643675
Novex-3	1378	4357;4358;4359	chr2:178778950;178778949;178778948	chr2:179643677;179643676;179643675

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-5
• Domain position: 88
• Structural Position: 173
• Q(SASA): 0.2536
• 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/E	None	None	0.999	N	0.615	0.488	0.435152311215	gnomAD-4.0.0	1.59089E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85714E-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	0.9745	likely_pathogenic	0.982	pathogenic	-1.061	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
K/C	0.9816	likely_pathogenic	0.9872	pathogenic	-1.044	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
K/D	0.9955	likely_pathogenic	0.9969	pathogenic	-0.431	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
K/E	0.9527	likely_pathogenic	0.9743	pathogenic	-0.232	Destabilizing	0.999	D	0.615	neutral	N	0.459422503	None	None	N
K/F	0.9875	likely_pathogenic	0.9907	pathogenic	-0.52	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
K/G	0.9886	likely_pathogenic	0.9921	pathogenic	-1.492	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
K/H	0.8694	likely_pathogenic	0.9186	pathogenic	-1.603	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
K/I	0.9074	likely_pathogenic	0.9111	pathogenic	0.105	Stabilizing	1.0	D	0.855	deleterious	N	0.502113448	None	None	N
K/L	0.9121	likely_pathogenic	0.9285	pathogenic	0.105	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
K/M	0.8575	likely_pathogenic	0.8922	pathogenic	-0.113	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
K/N	0.9822	likely_pathogenic	0.9885	pathogenic	-0.935	Destabilizing	1.0	D	0.746	deleterious	N	0.475259532	None	None	N
K/P	0.9967	likely_pathogenic	0.9975	pathogenic	-0.256	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
K/Q	0.8017	likely_pathogenic	0.9	pathogenic	-0.85	Destabilizing	1.0	D	0.745	deleterious	N	0.472675243	None	None	N
K/R	0.252	likely_benign	0.3426	ambiguous	-0.677	Destabilizing	0.999	D	0.553	neutral	N	0.413890663	None	None	N
K/S	0.9848	likely_pathogenic	0.991	pathogenic	-1.679	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	N
K/T	0.9185	likely_pathogenic	0.9376	pathogenic	-1.238	Destabilizing	1.0	D	0.797	deleterious	N	0.449797027	None	None	N
K/V	0.8999	likely_pathogenic	0.9116	pathogenic	-0.256	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
K/W	0.9898	likely_pathogenic	0.9937	pathogenic	-0.375	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
K/Y	0.9612	likely_pathogenic	0.9718	pathogenic	-0.078	Destabilizing	1.0	D	0.839	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.