TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8653	26182;26183;26184	chr2:178715229;178715228;178715227	chr2:179579956;179579955;179579954
N2AB	8336	25231;25232;25233	chr2:178715229;178715228;178715227	chr2:179579956;179579955;179579954
N2A	7409	22450;22451;22452	chr2:178715229;178715228;178715227	chr2:179579956;179579955;179579954
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-72
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.554
• 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/D	rs879235743	-0.246	0.345	N	0.487	0.101	0.277730125212	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
E/D	rs879235743	-0.246	0.345	N	0.487	0.101	0.277730125212	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs879235743	-0.246	0.345	N	0.487	0.101	0.277730125212	gnomAD-4.0.0	2.56592E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.79035E-06	0	0
E/G	None	None	0.979	N	0.499	0.504	0.570754586423	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
E/K	None	None	0.791	D	0.499	0.275	0.396494342077	gnomAD-4.0.0	1.60023E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86885E-06	0	0
E/Q	rs566740788	0.151	0.144	D	0.294	0.129	0.272639205421	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
E/Q	rs566740788	0.151	0.144	D	0.294	0.129	0.272639205421	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs566740788	0.151	0.144	D	0.294	0.129	0.272639205421	1000 genomes	1.99681E-04	None	None	None	None	I	None	8E-04	0	None	None	0	0	None	None	None	0	None
E/Q	rs566740788	0.151	0.144	D	0.294	0.129	0.272639205421	gnomAD-4.0.0	2.57369E-06	None	None	None	None	I	None	3.39305E-05	0	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
E/A	0.1382	likely_benign	0.1333	benign	-0.321	Destabilizing	0.804	D	0.501	neutral	N	0.517975448	None	None	I
E/C	0.8058	likely_pathogenic	0.8065	pathogenic	-0.002	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	I
E/D	0.1578	likely_benign	0.1561	benign	-0.357	Destabilizing	0.345	N	0.487	neutral	N	0.513993781	None	None	I
E/F	0.6653	likely_pathogenic	0.648	pathogenic	-0.247	Destabilizing	0.972	D	0.668	neutral	None	None	None	None	I
E/G	0.1669	likely_benign	0.1555	benign	-0.508	Destabilizing	0.979	D	0.499	neutral	N	0.495927134	None	None	I
E/H	0.3852	ambiguous	0.3643	ambiguous	0.016	Stabilizing	0.995	D	0.474	neutral	None	None	None	None	I
E/I	0.2988	likely_benign	0.301	benign	0.134	Stabilizing	0.892	D	0.638	neutral	None	None	None	None	I
E/K	0.1266	likely_benign	0.1233	benign	0.383	Stabilizing	0.791	D	0.499	neutral	D	0.522573192	None	None	I
E/L	0.3155	likely_benign	0.3101	benign	0.134	Stabilizing	0.033	N	0.395	neutral	None	None	None	None	I
E/M	0.3772	ambiguous	0.3796	ambiguous	0.199	Stabilizing	0.918	D	0.611	neutral	None	None	None	None	I
E/N	0.2581	likely_benign	0.2449	benign	0.08	Stabilizing	0.885	D	0.491	neutral	None	None	None	None	I
E/P	0.503	ambiguous	0.4559	ambiguous	0.002	Stabilizing	0.833	D	0.539	neutral	None	None	None	None	I
E/Q	0.1091	likely_benign	0.1013	benign	0.101	Stabilizing	0.144	N	0.294	neutral	D	0.529269878	None	None	I
E/R	0.2082	likely_benign	0.1977	benign	0.575	Stabilizing	0.946	D	0.487	neutral	None	None	None	None	I
E/S	0.1866	likely_benign	0.1734	benign	-0.074	Destabilizing	0.844	D	0.481	neutral	None	None	None	None	I
E/T	0.183	likely_benign	0.1801	benign	0.078	Stabilizing	0.963	D	0.488	neutral	None	None	None	None	I
E/V	0.1762	likely_benign	0.1787	benign	0.002	Stabilizing	0.558	D	0.499	neutral	N	0.494405155	None	None	I
E/W	0.8432	likely_pathogenic	0.8354	pathogenic	-0.114	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
E/Y	0.5302	ambiguous	0.5108	ambiguous	-0.002	Destabilizing	0.998	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.