TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33052	99379;99380;99381	chr2:178538675;178538674;178538673	chr2:179403402;179403401;179403400
N2AB	31411	94456;94457;94458	chr2:178538675;178538674;178538673	chr2:179403402;179403401;179403400
N2A	30484	91675;91676;91677	chr2:178538675;178538674;178538673	chr2:179403402;179403401;179403400
N2B	23987	72184;72185;72186	chr2:178538675;178538674;178538673	chr2:179403402;179403401;179403400
Novex-1	24112	72559;72560;72561	chr2:178538675;178538674;178538673	chr2:179403402;179403401;179403400
Novex-2	24179	72760;72761;72762	chr2:178538675;178538674;178538673	chr2:179403402;179403401;179403400
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: Fn3-129
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.2569
• 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	rs758109676	-1.13	1.0	N	0.785	0.306	0.420939154896	gnomAD-2.1.1	3.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.96091E-04	None	0	1.56E-05	1.40174E-04
R/C	rs758109676	-1.13	1.0	N	0.785	0.306	0.420939154896	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	1.47E-05	0	0
R/C	rs758109676	-1.13	1.0	N	0.785	0.306	0.420939154896	gnomAD-4.0.0	2.72693E-05	None	None	None	None	N	None	0	1.667E-05	None	0	0	None	0	0	2.54293E-05	1.31767E-04	1.60128E-05
R/H	rs72648276	-1.85	1.0	N	0.656	0.259	None	gnomAD-2.1.1	4.64E-05	None	None	None	None	N	None	8.27E-05	5.65E-05	None	0	0	None	1.96091E-04	None	0	1.56E-05	1.40174E-04
R/H	rs72648276	-1.85	1.0	N	0.656	0.259	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	1.47E-05	0	0
R/H	rs72648276	-1.85	1.0	N	0.656	0.259	None	gnomAD-4.0.0	1.92113E-05	None	None	None	None	N	None	5.34074E-05	5E-05	None	0	0	None	0	0	9.32415E-06	1.31749E-04	1.60128E-05
R/P	rs72648276	-0.624	0.999	N	0.784	0.356	0.37953744168	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
R/P	rs72648276	-0.624	0.999	N	0.784	0.356	0.37953744168	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/P	rs72648276	-0.624	0.999	N	0.784	0.356	0.37953744168	gnomAD-4.0.0	3.0986E-06	None	None	None	None	N	None	2.67037E-05	0	None	0	0	None	0	0	0	3.29374E-05	0
R/S	None	None	0.996	N	0.695	0.315	0.366848117066	gnomAD-4.0.0	6.84235E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99507E-07	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	0.7373	likely_pathogenic	0.7048	pathogenic	-0.461	Destabilizing	0.953	D	0.531	neutral	None	None	None	None	N
R/C	0.3298	likely_benign	0.2856	benign	-0.542	Destabilizing	1.0	D	0.785	deleterious	N	0.470082246	None	None	N
R/D	0.9549	likely_pathogenic	0.9509	pathogenic	-0.028	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
R/E	0.7406	likely_pathogenic	0.7084	pathogenic	0.126	Stabilizing	0.992	D	0.589	neutral	None	None	None	None	N
R/F	0.9043	likely_pathogenic	0.8852	pathogenic	-0.187	Destabilizing	0.986	D	0.797	deleterious	None	None	None	None	N
R/G	0.7009	likely_pathogenic	0.6622	pathogenic	-0.771	Destabilizing	0.999	D	0.691	prob.neutral	N	0.43753786	None	None	N
R/H	0.2829	likely_benign	0.2794	benign	-1.149	Destabilizing	1.0	D	0.656	neutral	N	0.478099191	None	None	N
R/I	0.5504	ambiguous	0.4769	ambiguous	0.369	Stabilizing	0.973	D	0.724	prob.delet.	None	None	None	None	N
R/K	0.1641	likely_benign	0.1638	benign	-0.339	Destabilizing	0.944	D	0.476	neutral	None	None	None	None	N
R/L	0.461	ambiguous	0.4117	ambiguous	0.369	Stabilizing	0.109	N	0.467	neutral	N	0.403620075	None	None	N
R/M	0.5907	likely_pathogenic	0.5255	ambiguous	-0.262	Destabilizing	0.986	D	0.753	deleterious	None	None	None	None	N
R/N	0.8735	likely_pathogenic	0.8654	pathogenic	-0.184	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
R/P	0.5588	ambiguous	0.5551	ambiguous	0.113	Stabilizing	0.999	D	0.784	deleterious	N	0.384879598	None	None	N
R/Q	0.2187	likely_benign	0.2025	benign	-0.173	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	N
R/S	0.9045	likely_pathogenic	0.8902	pathogenic	-0.747	Destabilizing	0.996	D	0.695	prob.neutral	N	0.441175598	None	None	N
R/T	0.7049	likely_pathogenic	0.6587	pathogenic	-0.402	Destabilizing	0.976	D	0.683	prob.neutral	None	None	None	None	N
R/V	0.6428	likely_pathogenic	0.5979	pathogenic	0.113	Stabilizing	0.91	D	0.706	prob.neutral	None	None	None	None	N
R/W	0.5494	ambiguous	0.5146	ambiguous	0.007	Stabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
R/Y	0.7593	likely_pathogenic	0.7326	pathogenic	0.301	Stabilizing	0.993	D	0.789	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.