TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33335	100228;100229;100230	chr2:178537106;178537105;178537104	chr2:179401833;179401832;179401831
N2AB	31694	95305;95306;95307	chr2:178537106;178537105;178537104	chr2:179401833;179401832;179401831
N2A	30767	92524;92525;92526	chr2:178537106;178537105;178537104	chr2:179401833;179401832;179401831
N2B	24270	73033;73034;73035	chr2:178537106;178537105;178537104	chr2:179401833;179401832;179401831
Novex-1	24395	73408;73409;73410	chr2:178537106;178537105;178537104	chr2:179401833;179401832;179401831
Novex-2	24462	73609;73610;73611	chr2:178537106;178537105;178537104	chr2:179401833;179401832;179401831
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: Fn3-130
• Domain position: 46
• Structural Position: 60
• Q(SASA): 0.7801
• 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/D	rs779632637	0.061	0.999	N	0.437	0.24	0.381746406553	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
E/D	rs779632637	0.061	0.999	N	0.437	0.24	0.381746406553	gnomAD-4.0.0	3.18546E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72001E-06	0	0
E/K	None	None	0.999	N	0.555	0.479	0.357929162469	gnomAD-4.0.0	4.10669E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59847E-06	0	3.31477E-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	0.1535	likely_benign	0.1362	benign	-0.04	Destabilizing	0.999	D	0.579	neutral	N	0.452758029	None	None	N
E/C	0.8929	likely_pathogenic	0.8756	pathogenic	-0.474	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
E/D	0.1319	likely_benign	0.1204	benign	-0.601	Destabilizing	0.999	D	0.437	neutral	N	0.464473746	None	None	N
E/F	0.8378	likely_pathogenic	0.8251	pathogenic	-0.162	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/G	0.1976	likely_benign	0.1883	benign	-0.104	Destabilizing	1.0	D	0.588	neutral	N	0.445733269	None	None	N
E/H	0.5949	likely_pathogenic	0.553	ambiguous	0.544	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/I	0.4587	ambiguous	0.4214	ambiguous	0.07	Stabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
E/K	0.1839	likely_benign	0.1572	benign	0.117	Stabilizing	0.999	D	0.555	neutral	N	0.418048023	None	None	N
E/L	0.5263	ambiguous	0.4741	ambiguous	0.07	Stabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
E/M	0.6261	likely_pathogenic	0.5751	pathogenic	-0.226	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/N	0.2743	likely_benign	0.2499	benign	-0.052	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
E/P	0.3866	ambiguous	0.2843	benign	0.047	Stabilizing	1.0	D	0.634	neutral	None	None	None	None	N
E/Q	0.2242	likely_benign	0.2075	benign	-0.071	Destabilizing	1.0	D	0.561	neutral	N	0.460742794	None	None	N
E/R	0.331	likely_benign	0.3073	benign	0.359	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
E/S	0.2187	likely_benign	0.2007	benign	-0.183	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
E/T	0.2548	likely_benign	0.2272	benign	-0.119	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	N
E/V	0.2724	likely_benign	0.2465	benign	0.047	Stabilizing	1.0	D	0.639	neutral	N	0.487025318	None	None	N
E/W	0.9354	likely_pathogenic	0.9221	pathogenic	-0.159	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
E/Y	0.7047	likely_pathogenic	0.6692	pathogenic	0.034	Stabilizing	1.0	D	0.684	prob.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.