TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15800	47623;47624;47625	chr2:178617953;178617952;178617951	chr2:179482680;179482679;179482678
N2AB	14159	42700;42701;42702	chr2:178617953;178617952;178617951	chr2:179482680;179482679;179482678
N2A	13232	39919;39920;39921	chr2:178617953;178617952;178617951	chr2:179482680;179482679;179482678
N2B	6735	20428;20429;20430	chr2:178617953;178617952;178617951	chr2:179482680;179482679;179482678
Novex-1	6860	20803;20804;20805	chr2:178617953;178617952;178617951	chr2:179482680;179482679;179482678
Novex-2	6927	21004;21005;21006	chr2:178617953;178617952;178617951	chr2:179482680;179482679;179482678
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: Fn3-2
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.5959
• 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	rs114145817	0.386	0.801	N	0.394	0.21	0.181679512989	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
K/N	rs114145817	0.386	0.801	N	0.394	0.21	0.181679512989	gnomAD-4.0.0	1.50613E-05	None	None	None	None	N	None	2.99401E-05	0	None	0	0	None	0	0	1.70984E-05	0	3.31664E-05

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	0.5813	likely_pathogenic	0.6097	pathogenic	-0.559	Destabilizing	0.688	D	0.441	neutral	None	None	None	None	N
K/C	0.8704	likely_pathogenic	0.8641	pathogenic	-0.548	Destabilizing	0.998	D	0.553	neutral	None	None	None	None	N
K/D	0.8449	likely_pathogenic	0.8632	pathogenic	0.146	Stabilizing	0.915	D	0.439	neutral	None	None	None	None	N
K/E	0.3715	ambiguous	0.3999	ambiguous	0.222	Stabilizing	0.625	D	0.435	neutral	N	0.476519691	None	None	N
K/F	0.9307	likely_pathogenic	0.939	pathogenic	-0.47	Destabilizing	0.991	D	0.537	neutral	None	None	None	None	N
K/G	0.6594	likely_pathogenic	0.671	pathogenic	-0.872	Destabilizing	0.915	D	0.518	neutral	None	None	None	None	N
K/H	0.5389	ambiguous	0.5557	ambiguous	-1.229	Destabilizing	0.974	D	0.45	neutral	None	None	None	None	N
K/I	0.6447	likely_pathogenic	0.6524	pathogenic	0.228	Stabilizing	0.974	D	0.544	neutral	None	None	None	None	N
K/L	0.673	likely_pathogenic	0.69	pathogenic	0.228	Stabilizing	0.842	D	0.518	neutral	None	None	None	None	N
K/M	0.5092	ambiguous	0.5202	ambiguous	0.166	Stabilizing	0.989	D	0.448	neutral	D	0.524737777	None	None	N
K/N	0.7193	likely_pathogenic	0.754	pathogenic	-0.218	Destabilizing	0.801	D	0.394	neutral	N	0.48570977	None	None	N
K/P	0.8235	likely_pathogenic	0.8382	pathogenic	-0.004	Destabilizing	0.991	D	0.451	neutral	None	None	None	None	N
K/Q	0.221	likely_benign	0.2348	benign	-0.356	Destabilizing	0.801	D	0.442	neutral	N	0.4825142	None	None	N
K/R	0.0833	likely_benign	0.0822	benign	-0.407	Destabilizing	0.002	N	0.171	neutral	N	0.449423591	None	None	N
K/S	0.67	likely_pathogenic	0.6922	pathogenic	-0.922	Destabilizing	0.842	D	0.384	neutral	None	None	None	None	N
K/T	0.4297	ambiguous	0.4509	ambiguous	-0.648	Destabilizing	0.891	D	0.427	neutral	N	0.462988949	None	None	N
K/V	0.6044	likely_pathogenic	0.6112	pathogenic	-0.004	Destabilizing	0.974	D	0.516	neutral	None	None	None	None	N
K/W	0.9185	likely_pathogenic	0.9109	pathogenic	-0.324	Destabilizing	0.998	D	0.602	neutral	None	None	None	None	N
K/Y	0.8514	likely_pathogenic	0.8609	pathogenic	-0.018	Destabilizing	0.991	D	0.538	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.