TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15796	47611;47612;47613	chr2:178617965;178617964;178617963	chr2:179482692;179482691;179482690
N2AB	14155	42688;42689;42690	chr2:178617965;178617964;178617963	chr2:179482692;179482691;179482690
N2A	13228	39907;39908;39909	chr2:178617965;178617964;178617963	chr2:179482692;179482691;179482690
N2B	6731	20416;20417;20418	chr2:178617965;178617964;178617963	chr2:179482692;179482691;179482690
Novex-1	6856	20791;20792;20793	chr2:178617965;178617964;178617963	chr2:179482692;179482691;179482690
Novex-2	6923	20992;20993;20994	chr2:178617965;178617964;178617963	chr2:179482692;179482691;179482690
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-2
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.135
• 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
E/K	rs2057656549	None	0.992	D	0.639	0.44	0.359763055319	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
E/K	rs2057656549	None	0.992	D	0.639	0.44	0.359763055319	gnomAD-4.0.0	6.58553E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07211E-04	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
E/A	0.907	likely_pathogenic	0.8925	pathogenic	-2.431	Highly Destabilizing	0.996	D	0.659	neutral	D	0.690760174	None	None	N
E/C	0.9911	likely_pathogenic	0.9893	pathogenic	-1.45	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/D	0.8676	likely_pathogenic	0.8626	pathogenic	-1.828	Destabilizing	0.996	D	0.622	neutral	D	0.577303043	None	None	N
E/F	0.9917	likely_pathogenic	0.9915	pathogenic	-2.162	Highly Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
E/G	0.9392	likely_pathogenic	0.9287	pathogenic	-2.778	Highly Destabilizing	0.999	D	0.745	deleterious	D	0.70952083	None	None	N
E/H	0.979	likely_pathogenic	0.9779	pathogenic	-1.949	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
E/I	0.9728	likely_pathogenic	0.9715	pathogenic	-1.411	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
E/K	0.9718	likely_pathogenic	0.9692	pathogenic	-2.334	Highly Destabilizing	0.992	D	0.639	neutral	D	0.617848257	None	None	N
E/L	0.9737	likely_pathogenic	0.9744	pathogenic	-1.411	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/M	0.9724	likely_pathogenic	0.9708	pathogenic	-0.571	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/N	0.9843	likely_pathogenic	0.9822	pathogenic	-2.36	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/P	0.9993	likely_pathogenic	0.9993	pathogenic	-1.742	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/Q	0.7049	likely_pathogenic	0.6982	pathogenic	-2.099	Highly Destabilizing	0.957	D	0.328	neutral	N	0.499308879	None	None	N
E/R	0.9666	likely_pathogenic	0.9648	pathogenic	-2.016	Highly Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
E/S	0.9265	likely_pathogenic	0.915	pathogenic	-3.097	Highly Destabilizing	0.997	D	0.691	prob.neutral	None	None	None	None	N
E/T	0.9628	likely_pathogenic	0.9603	pathogenic	-2.764	Highly Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/V	0.9389	likely_pathogenic	0.9349	pathogenic	-1.742	Destabilizing	0.999	D	0.767	deleterious	D	0.670208319	None	None	N
E/W	0.9976	likely_pathogenic	0.9975	pathogenic	-2.186	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/Y	0.9901	likely_pathogenic	0.9897	pathogenic	-2.022	Highly Destabilizing	1.0	D	0.814	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.