TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31761	95506;95507;95508	chr2:178545955;178545954;178545953	chr2:179410682;179410681;179410680
N2AB	30120	90583;90584;90585	chr2:178545955;178545954;178545953	chr2:179410682;179410681;179410680
N2A	29193	87802;87803;87804	chr2:178545955;178545954;178545953	chr2:179410682;179410681;179410680
N2B	22696	68311;68312;68313	chr2:178545955;178545954;178545953	chr2:179410682;179410681;179410680
Novex-1	22821	68686;68687;68688	chr2:178545955;178545954;178545953	chr2:179410682;179410681;179410680
Novex-2	22888	68887;68888;68889	chr2:178545955;178545954;178545953	chr2:179410682;179410681;179410680
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-119
• Domain position: 54
• Structural Position: 75
• Q(SASA): 0.4759
• 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/K	rs727505342	-0.117	1.0	N	0.574	0.411	0.332646915603	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	1.78E-05	0
E/K	rs727505342	-0.117	1.0	N	0.574	0.411	0.332646915603	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs727505342	-0.117	1.0	N	0.574	0.411	0.332646915603	gnomAD-4.0.0	9.29459E-06	None	None	None	None	I	None	2.66539E-05	1.6665E-05	None	0	0	None	0	1.64962E-04	7.62842E-06	2.19578E-05	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	0.1206	likely_benign	0.1158	benign	-0.579	Destabilizing	0.999	D	0.648	neutral	N	0.479019123	None	None	I
E/C	0.7188	likely_pathogenic	0.688	pathogenic	-0.261	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
E/D	0.118	likely_benign	0.1027	benign	-0.399	Destabilizing	0.999	D	0.422	neutral	N	0.410369902	None	None	I
E/F	0.597	likely_pathogenic	0.5633	ambiguous	-0.373	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
E/G	0.1745	likely_benign	0.1496	benign	-0.81	Destabilizing	1.0	D	0.623	neutral	N	0.454950185	None	None	I
E/H	0.3535	ambiguous	0.3214	benign	-0.242	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
E/I	0.2402	likely_benign	0.2379	benign	0.014	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
E/K	0.1272	likely_benign	0.1171	benign	-0.186	Destabilizing	1.0	D	0.574	neutral	N	0.45983593	None	None	I
E/L	0.324	likely_benign	0.3049	benign	0.014	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
E/M	0.35	ambiguous	0.3392	benign	0.151	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	I
E/N	0.1643	likely_benign	0.1414	benign	-0.357	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
E/P	0.4859	ambiguous	0.503	ambiguous	-0.163	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
E/Q	0.1146	likely_benign	0.1106	benign	-0.306	Destabilizing	1.0	D	0.61	neutral	N	0.493623217	None	None	I
E/R	0.2164	likely_benign	0.2053	benign	0.123	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
E/S	0.1438	likely_benign	0.1284	benign	-0.606	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	I
E/T	0.156	likely_benign	0.149	benign	-0.429	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
E/V	0.1551	likely_benign	0.156	benign	-0.163	Destabilizing	1.0	D	0.672	neutral	N	0.490505554	None	None	I
E/W	0.862	likely_pathogenic	0.8451	pathogenic	-0.209	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
E/Y	0.4896	ambiguous	0.4512	ambiguous	-0.154	Destabilizing	1.0	D	0.66	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.