TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24283	73072;73073;73074	chr2:178573285;178573284;178573283	chr2:179438012;179438011;179438010
N2AB	22642	68149;68150;68151	chr2:178573285;178573284;178573283	chr2:179438012;179438011;179438010
N2A	21715	65368;65369;65370	chr2:178573285;178573284;178573283	chr2:179438012;179438011;179438010
N2B	15218	45877;45878;45879	chr2:178573285;178573284;178573283	chr2:179438012;179438011;179438010
Novex-1	15343	46252;46253;46254	chr2:178573285;178573284;178573283	chr2:179438012;179438011;179438010
Novex-2	15410	46453;46454;46455	chr2:178573285;178573284;178573283	chr2:179438012;179438011;179438010
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: Fn3-64
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.4986
• 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	None	None	0.967	N	0.641	0.19	0.247322355667	gnomAD-4.0.0	1.64151E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.93474E-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	0.8318	likely_pathogenic	0.8501	pathogenic	-0.456	Destabilizing	0.916	D	0.61	neutral	None	None	None	None	N
K/C	0.8852	likely_pathogenic	0.9089	pathogenic	-0.538	Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
K/D	0.9572	likely_pathogenic	0.9604	pathogenic	0.326	Stabilizing	0.987	D	0.719	prob.delet.	None	None	None	None	N
K/E	0.7123	likely_pathogenic	0.7452	pathogenic	0.397	Stabilizing	0.892	D	0.53	neutral	N	0.494391221	None	None	N
K/F	0.9605	likely_pathogenic	0.9624	pathogenic	-0.426	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
K/G	0.9138	likely_pathogenic	0.9252	pathogenic	-0.743	Destabilizing	0.975	D	0.68	prob.neutral	None	None	None	None	N
K/H	0.5306	ambiguous	0.5639	ambiguous	-1.018	Destabilizing	0.997	D	0.699	prob.neutral	None	None	None	None	N
K/I	0.7335	likely_pathogenic	0.7517	pathogenic	0.249	Stabilizing	0.983	D	0.735	prob.delet.	N	0.475963914	None	None	N
K/L	0.7291	likely_pathogenic	0.76	pathogenic	0.249	Stabilizing	0.975	D	0.68	prob.neutral	None	None	None	None	N
K/M	0.6167	likely_pathogenic	0.6513	pathogenic	0.088	Stabilizing	0.999	D	0.688	prob.neutral	None	None	None	None	N
K/N	0.9127	likely_pathogenic	0.918	pathogenic	-0.135	Destabilizing	0.967	D	0.641	neutral	N	0.514574492	None	None	N
K/P	0.9302	likely_pathogenic	0.9477	pathogenic	0.044	Stabilizing	0.996	D	0.725	prob.delet.	None	None	None	None	N
K/Q	0.3784	ambiguous	0.4202	ambiguous	-0.237	Destabilizing	0.967	D	0.633	neutral	N	0.49167899	None	None	N
K/R	0.0813	likely_benign	0.0854	benign	-0.278	Destabilizing	0.025	N	0.251	neutral	N	0.420106893	None	None	N
K/S	0.8931	likely_pathogenic	0.9051	pathogenic	-0.823	Destabilizing	0.916	D	0.589	neutral	None	None	None	None	N
K/T	0.5737	likely_pathogenic	0.6184	pathogenic	-0.557	Destabilizing	0.967	D	0.715	prob.delet.	N	0.456214048	None	None	N
K/V	0.6809	likely_pathogenic	0.7074	pathogenic	0.044	Stabilizing	0.987	D	0.733	prob.delet.	None	None	None	None	N
K/W	0.917	likely_pathogenic	0.9304	pathogenic	-0.313	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
K/Y	0.8861	likely_pathogenic	0.8914	pathogenic	-0.001	Destabilizing	0.996	D	0.741	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.