TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32869	98830;98831;98832	chr2:178539460;178539459;178539458	chr2:179404187;179404186;179404185
N2AB	31228	93907;93908;93909	chr2:178539460;178539459;178539458	chr2:179404187;179404186;179404185
N2A	30301	91126;91127;91128	chr2:178539460;178539459;178539458	chr2:179404187;179404186;179404185
N2B	23804	71635;71636;71637	chr2:178539460;178539459;178539458	chr2:179404187;179404186;179404185
Novex-1	23929	72010;72011;72012	chr2:178539460;178539459;178539458	chr2:179404187;179404186;179404185
Novex-2	23996	72211;72212;72213	chr2:178539460;178539459;178539458	chr2:179404187;179404186;179404185
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-127
• Domain position: 75
• Structural Position: 107
• Q(SASA): 0.1485
• 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
R/C	rs186244950	-1.569	1.0	D	0.726	0.516	None	gnomAD-2.1.1	2.14021E-04	None	None	None	None	N	None	2.47954E-04	0	None	2.8041E-03	0	None	3.92182E-04	None	0	8.58E-05	2.80348E-04
R/C	rs186244950	-1.569	1.0	D	0.726	0.516	None	gnomAD-3.1.2	1.2489E-04	None	None	None	None	N	None	1.69E-04	6.54E-05	0	2.30814E-03	0	None	0	0	4.41E-05	0	0
R/C	rs186244950	-1.569	1.0	D	0.726	0.516	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
R/C	rs186244950	-1.569	1.0	D	0.726	0.516	None	gnomAD-4.0.0	1.19593E-04	None	None	None	None	N	None	2.533E-04	1.66611E-05	None	2.29761E-03	0	None	0	0	4.06858E-05	4.83092E-04	2.0808E-04
R/H	rs587780495	-2.051	1.0	N	0.58	0.433	0.324161360171	gnomAD-2.1.1	4.64E-05	None	None	None	None	N	None	0	0	None	0	1.0248E-04	None	2.94137E-04	None	0	7.8E-06	1.40135E-04
R/H	rs587780495	-2.051	1.0	N	0.58	0.433	0.324161360171	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	0	6.54E-05	0	0	1.92456E-04	None	0	0	2.94E-05	8.28157E-04	0
R/H	rs587780495	-2.051	1.0	N	0.58	0.433	0.324161360171	gnomAD-4.0.0	2.78837E-05	None	None	None	None	N	None	0	1.66617E-05	None	0	6.68479E-05	None	0	3.30142E-04	5.93327E-06	3.18394E-04	4.80169E-05
R/L	None	None	0.992	N	0.553	0.396	0.639907133395	gnomAD-4.0.0	1.3684E-06	None	None	None	None	N	None	0	4.47247E-05	None	0	0	None	0	0	0	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
R/A	0.8292	likely_pathogenic	0.7671	pathogenic	-1.788	Destabilizing	0.97	D	0.52	neutral	None	None	None	None	N
R/C	0.3424	ambiguous	0.283	benign	-1.727	Destabilizing	1.0	D	0.726	prob.delet.	D	0.528067271	None	None	N
R/D	0.9899	likely_pathogenic	0.9851	pathogenic	-0.97	Destabilizing	0.996	D	0.603	neutral	None	None	None	None	N
R/E	0.873	likely_pathogenic	0.8269	pathogenic	-0.746	Destabilizing	0.97	D	0.517	neutral	None	None	None	None	N
R/F	0.9119	likely_pathogenic	0.8817	pathogenic	-0.886	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
R/G	0.8391	likely_pathogenic	0.7752	pathogenic	-2.144	Highly Destabilizing	0.992	D	0.553	neutral	D	0.527560292	None	None	N
R/H	0.2986	likely_benign	0.2662	benign	-1.915	Destabilizing	1.0	D	0.58	neutral	N	0.516203986	None	None	N
R/I	0.6869	likely_pathogenic	0.633	pathogenic	-0.754	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
R/K	0.2388	likely_benign	0.2074	benign	-1.223	Destabilizing	0.155	N	0.269	neutral	None	None	None	None	N
R/L	0.6301	likely_pathogenic	0.5601	ambiguous	-0.754	Destabilizing	0.992	D	0.553	neutral	N	0.508188589	None	None	N
R/M	0.6906	likely_pathogenic	0.6172	pathogenic	-1.301	Destabilizing	1.0	D	0.632	neutral	None	None	None	None	N
R/N	0.961	likely_pathogenic	0.9476	pathogenic	-1.334	Destabilizing	0.996	D	0.521	neutral	None	None	None	None	N
R/P	0.9963	likely_pathogenic	0.9965	pathogenic	-1.087	Destabilizing	0.999	D	0.681	prob.neutral	D	0.539334671	None	None	N
R/Q	0.2327	likely_benign	0.1945	benign	-1.126	Destabilizing	0.991	D	0.547	neutral	None	None	None	None	N
R/S	0.8934	likely_pathogenic	0.8497	pathogenic	-2.142	Highly Destabilizing	0.984	D	0.519	neutral	N	0.496071815	None	None	N
R/T	0.7586	likely_pathogenic	0.6953	pathogenic	-1.705	Destabilizing	0.985	D	0.523	neutral	None	None	None	None	N
R/V	0.7502	likely_pathogenic	0.6903	pathogenic	-1.087	Destabilizing	0.996	D	0.675	neutral	None	None	None	None	N
R/W	0.545	ambiguous	0.4801	ambiguous	-0.451	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
R/Y	0.8314	likely_pathogenic	0.7877	pathogenic	-0.309	Destabilizing	0.999	D	0.701	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.