TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31095	93508;93509;93510	chr2:178548343;178548342;178548341	chr2:179413070;179413069;179413068
N2AB	29454	88585;88586;88587	chr2:178548343;178548342;178548341	chr2:179413070;179413069;179413068
N2A	28527	85804;85805;85806	chr2:178548343;178548342;178548341	chr2:179413070;179413069;179413068
N2B	22030	66313;66314;66315	chr2:178548343;178548342;178548341	chr2:179413070;179413069;179413068
Novex-1	22155	66688;66689;66690	chr2:178548343;178548342;178548341	chr2:179413070;179413069;179413068
Novex-2	22222	66889;66890;66891	chr2:178548343;178548342;178548341	chr2:179413070;179413069;179413068
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-114
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.755
• 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
E/G	rs1235567368	None	0.989	N	0.543	0.537	0.405560941015	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs1235567368	None	0.989	N	0.543	0.537	0.405560941015	gnomAD-4.0.0	2.56201E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.7856E-06	0	0
E/K	None	None	0.956	N	0.517	0.248	0.275215494804	gnomAD-4.0.0	3.18228E-06	None	None	None	None	I	None	0	0	None	0	2.77254E-05	None	0	0	0	0	3.02371E-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
E/A	0.3013	likely_benign	0.2695	benign	-0.619	Destabilizing	0.978	D	0.543	neutral	N	0.516401289	None	None	I
E/C	0.9523	likely_pathogenic	0.9373	pathogenic	-0.282	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
E/D	0.2799	likely_benign	0.2265	benign	-0.395	Destabilizing	0.948	D	0.454	neutral	N	0.509822033	None	None	I
E/F	0.9477	likely_pathogenic	0.9238	pathogenic	-0.322	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	I
E/G	0.4848	ambiguous	0.4221	ambiguous	-0.848	Destabilizing	0.989	D	0.543	neutral	N	0.488958698	None	None	I
E/H	0.79	likely_pathogenic	0.7451	pathogenic	-0.063	Destabilizing	0.998	D	0.433	neutral	None	None	None	None	I
E/I	0.5525	ambiguous	0.4708	ambiguous	-0.034	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	I
E/K	0.3514	ambiguous	0.3077	benign	-0.037	Destabilizing	0.956	D	0.517	neutral	N	0.477325613	None	None	I
E/L	0.7327	likely_pathogenic	0.6454	pathogenic	-0.034	Destabilizing	0.995	D	0.558	neutral	None	None	None	None	I
E/M	0.7117	likely_pathogenic	0.6413	pathogenic	0.082	Stabilizing	1.0	D	0.614	neutral	None	None	None	None	I
E/N	0.5489	ambiguous	0.4794	ambiguous	-0.345	Destabilizing	0.998	D	0.455	neutral	None	None	None	None	I
E/P	0.7848	likely_pathogenic	0.6804	pathogenic	-0.209	Destabilizing	0.999	D	0.521	neutral	None	None	None	None	I
E/Q	0.2452	likely_benign	0.2176	benign	-0.283	Destabilizing	0.63	D	0.241	neutral	N	0.47382432	None	None	I
E/R	0.526	ambiguous	0.4659	ambiguous	0.307	Stabilizing	0.983	D	0.471	neutral	None	None	None	None	I
E/S	0.4266	ambiguous	0.3703	ambiguous	-0.564	Destabilizing	0.983	D	0.493	neutral	None	None	None	None	I
E/T	0.4526	ambiguous	0.3875	ambiguous	-0.376	Destabilizing	0.992	D	0.519	neutral	None	None	None	None	I
E/V	0.4103	ambiguous	0.3461	ambiguous	-0.209	Destabilizing	0.997	D	0.521	neutral	N	0.479433407	None	None	I
E/W	0.9884	likely_pathogenic	0.9821	pathogenic	-0.1	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
E/Y	0.8927	likely_pathogenic	0.8594	pathogenic	-0.075	Destabilizing	0.999	D	0.625	neutral	None	None	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.