TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24967	75124;75125;75126	chr2:178571233;178571232;178571231	chr2:179435960;179435959;179435958
N2AB	23326	70201;70202;70203	chr2:178571233;178571232;178571231	chr2:179435960;179435959;179435958
N2A	22399	67420;67421;67422	chr2:178571233;178571232;178571231	chr2:179435960;179435959;179435958
N2B	15902	47929;47930;47931	chr2:178571233;178571232;178571231	chr2:179435960;179435959;179435958
Novex-1	16027	48304;48305;48306	chr2:178571233;178571232;178571231	chr2:179435960;179435959;179435958
Novex-2	16094	48505;48506;48507	chr2:178571233;178571232;178571231	chr2:179435960;179435959;179435958
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: Fn3-69
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.2871
• 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/T	None	None	0.051	N	0.421	0.184	0.1749357433	gnomAD-4.0.0	1.59177E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85925E-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	0.196	likely_benign	0.2015	benign	-0.458	Destabilizing	0.525	D	0.397	neutral	None	None	None	None	N
K/C	0.3113	likely_benign	0.3179	benign	-0.571	Destabilizing	0.998	D	0.563	neutral	None	None	None	None	N
K/D	0.4965	ambiguous	0.4994	ambiguous	-0.176	Destabilizing	0.842	D	0.461	neutral	None	None	None	None	N
K/E	0.1719	likely_benign	0.1734	benign	-0.047	Destabilizing	0.625	D	0.354	neutral	N	0.381105787	None	None	N
K/F	0.4918	ambiguous	0.5089	ambiguous	0.007	Stabilizing	0.974	D	0.562	neutral	None	None	None	None	N
K/G	0.3122	likely_benign	0.3169	benign	-0.837	Destabilizing	0.842	D	0.486	neutral	None	None	None	None	N
K/H	0.1494	likely_benign	0.1537	benign	-1.033	Destabilizing	0.037	N	0.355	neutral	None	None	None	None	N
K/I	0.19	likely_benign	0.1983	benign	0.528	Stabilizing	0.949	D	0.564	neutral	None	None	None	None	N
K/L	0.2312	likely_benign	0.2398	benign	0.528	Stabilizing	0.728	D	0.486	neutral	None	None	None	None	N
K/M	0.1569	likely_benign	0.1615	benign	0.183	Stabilizing	0.989	D	0.535	neutral	N	0.476480251	None	None	N
K/N	0.2727	likely_benign	0.285	benign	-0.54	Destabilizing	0.801	D	0.332	neutral	N	0.442578321	None	None	N
K/P	0.8987	likely_pathogenic	0.8929	pathogenic	0.23	Stabilizing	0.974	D	0.555	neutral	None	None	None	None	N
K/Q	0.1004	likely_benign	0.1029	benign	-0.519	Destabilizing	0.801	D	0.401	neutral	N	0.406137518	None	None	N
K/R	0.0632	likely_benign	0.0626	benign	-0.631	Destabilizing	0.005	N	0.182	neutral	N	0.377257406	None	None	N
K/S	0.224	likely_benign	0.2325	benign	-1.116	Destabilizing	0.728	D	0.345	neutral	None	None	None	None	N
K/T	0.0965	likely_benign	0.0984	benign	-0.779	Destabilizing	0.051	N	0.421	neutral	N	0.395245734	None	None	N
K/V	0.1695	likely_benign	0.1727	benign	0.23	Stabilizing	0.728	D	0.525	neutral	None	None	None	None	N
K/W	0.4975	ambiguous	0.5092	ambiguous	0.079	Stabilizing	0.998	D	0.574	neutral	None	None	None	None	N
K/Y	0.3547	ambiguous	0.3682	ambiguous	0.342	Stabilizing	0.949	D	0.569	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.