TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17732	53419;53420;53421	chr2:178607494;178607493;178607492	chr2:179472221;179472220;179472219
N2AB	16091	48496;48497;48498	chr2:178607494;178607493;178607492	chr2:179472221;179472220;179472219
N2A	15164	45715;45716;45717	chr2:178607494;178607493;178607492	chr2:179472221;179472220;179472219
N2B	8667	26224;26225;26226	chr2:178607494;178607493;178607492	chr2:179472221;179472220;179472219
Novex-1	8792	26599;26600;26601	chr2:178607494;178607493;178607492	chr2:179472221;179472220;179472219
Novex-2	8859	26800;26801;26802	chr2:178607494;178607493;178607492	chr2:179472221;179472220;179472219
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: Ig-113
• Domain position: 56
• Structural Position: 141
• Q(SASA): 0.5009
• 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/R	rs2055177922	None	0.946	N	0.433	0.261	0.415690173769	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
K/R	rs2055177922	None	0.946	N	0.433	0.261	0.415690173769	gnomAD-4.0.0	6.57808E-06	None	None	None	None	N	None	0	6.5591E-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	0.4079	ambiguous	0.4204	ambiguous	-0.094	Destabilizing	0.851	D	0.486	neutral	None	None	None	None	N
K/C	0.763	likely_pathogenic	0.7306	pathogenic	-0.244	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
K/D	0.6028	likely_pathogenic	0.6475	pathogenic	0.227	Stabilizing	0.034	N	0.286	neutral	None	None	None	None	N
K/E	0.1976	likely_benign	0.2086	benign	0.261	Stabilizing	0.811	D	0.487	neutral	N	0.472952448	None	None	N
K/F	0.8608	likely_pathogenic	0.8486	pathogenic	-0.194	Destabilizing	0.988	D	0.639	neutral	None	None	None	None	N
K/G	0.5129	ambiguous	0.5284	ambiguous	-0.339	Destabilizing	0.959	D	0.494	neutral	None	None	None	None	N
K/H	0.357	ambiguous	0.3448	ambiguous	-0.661	Destabilizing	0.999	D	0.542	neutral	None	None	None	None	N
K/I	0.4807	ambiguous	0.4471	ambiguous	0.483	Stabilizing	0.952	D	0.539	neutral	None	None	None	None	N
K/L	0.4701	ambiguous	0.4517	ambiguous	0.483	Stabilizing	0.851	D	0.506	neutral	None	None	None	None	N
K/M	0.3456	ambiguous	0.3226	benign	0.28	Stabilizing	0.996	D	0.537	neutral	N	0.487747153	None	None	N
K/N	0.42	ambiguous	0.4377	ambiguous	0.168	Stabilizing	0.968	D	0.446	neutral	N	0.512068196	None	None	N
K/P	0.5485	ambiguous	0.5728	pathogenic	0.32	Stabilizing	0.996	D	0.542	neutral	None	None	None	None	N
K/Q	0.1638	likely_benign	0.1532	benign	0.027	Stabilizing	0.984	D	0.501	neutral	N	0.51068133	None	None	N
K/R	0.0974	likely_benign	0.0932	benign	-0.109	Destabilizing	0.946	D	0.433	neutral	N	0.474915318	None	None	N
K/S	0.4401	ambiguous	0.4511	ambiguous	-0.395	Destabilizing	0.919	D	0.454	neutral	None	None	None	None	N
K/T	0.1787	likely_benign	0.1769	benign	-0.189	Destabilizing	0.896	D	0.483	neutral	N	0.461794092	None	None	N
K/V	0.4192	ambiguous	0.383	ambiguous	0.32	Stabilizing	0.076	N	0.316	neutral	None	None	None	None	N
K/W	0.8314	likely_pathogenic	0.8044	pathogenic	-0.165	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
K/Y	0.7401	likely_pathogenic	0.7268	pathogenic	0.181	Stabilizing	0.996	D	0.605	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.