TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30935	93028;93029;93030	chr2:178548823;178548822;178548821	chr2:179413550;179413549;179413548
N2AB	29294	88105;88106;88107	chr2:178548823;178548822;178548821	chr2:179413550;179413549;179413548
N2A	28367	85324;85325;85326	chr2:178548823;178548822;178548821	chr2:179413550;179413549;179413548
N2B	21870	65833;65834;65835	chr2:178548823;178548822;178548821	chr2:179413550;179413549;179413548
Novex-1	21995	66208;66209;66210	chr2:178548823;178548822;178548821	chr2:179413550;179413549;179413548
Novex-2	22062	66409;66410;66411	chr2:178548823;178548822;178548821	chr2:179413550;179413549;179413548
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-150
• Domain position: 9
• Structural Position: 13
• Q(SASA): 0.4927
• Predicted PPI site: I

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
H/L	None	None	1.0	N	0.704	0.498	0.690638299042	gnomAD-4.0.0	1.59358E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85807E-06	0	0
H/Q	None	None	1.0	N	0.584	0.366	0.218112801441	gnomAD-4.0.0	3.42314E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49725E-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
H/A	0.6301	likely_pathogenic	0.6614	pathogenic	-1.347	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	I
H/C	0.3159	likely_benign	0.3238	benign	-0.468	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
H/D	0.7696	likely_pathogenic	0.8042	pathogenic	-1.199	Destabilizing	1.0	D	0.645	neutral	N	0.499445616	None	None	I
H/E	0.7212	likely_pathogenic	0.7363	pathogenic	-1.025	Destabilizing	0.999	D	0.439	neutral	None	None	None	None	I
H/F	0.4666	ambiguous	0.4704	ambiguous	0.467	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	I
H/G	0.8406	likely_pathogenic	0.8634	pathogenic	-1.783	Destabilizing	0.999	D	0.602	neutral	None	None	None	None	I
H/I	0.4035	ambiguous	0.4138	ambiguous	-0.08	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
H/K	0.6783	likely_pathogenic	0.6917	pathogenic	-0.784	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
H/L	0.175	likely_benign	0.1809	benign	-0.08	Destabilizing	1.0	D	0.704	prob.neutral	N	0.361376381	None	None	I
H/M	0.5809	likely_pathogenic	0.576	pathogenic	-0.305	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	I
H/N	0.3261	likely_benign	0.375	ambiguous	-1.309	Destabilizing	0.999	D	0.439	neutral	N	0.517858018	None	None	I
H/P	0.8448	likely_pathogenic	0.8735	pathogenic	-0.488	Destabilizing	1.0	D	0.695	prob.neutral	N	0.517858018	None	None	I
H/Q	0.4552	ambiguous	0.4842	ambiguous	-0.956	Destabilizing	1.0	D	0.584	neutral	N	0.424774499	None	None	I
H/R	0.3861	ambiguous	0.4045	ambiguous	-1.235	Destabilizing	1.0	D	0.583	neutral	N	0.474413885	None	None	I
H/S	0.6029	likely_pathogenic	0.6366	pathogenic	-1.377	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	I
H/T	0.5863	likely_pathogenic	0.6198	pathogenic	-1.076	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
H/V	0.3326	likely_benign	0.3356	benign	-0.488	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
H/W	0.636	likely_pathogenic	0.6239	pathogenic	1.026	Stabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
H/Y	0.1585	likely_benign	0.1694	benign	0.876	Stabilizing	0.999	D	0.463	neutral	N	0.433375339	None	None	I

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.