TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29373	88342;88343;88344	chr2:178557037;178557036;178557035	chr2:179421764;179421763;179421762
N2AB	27732	83419;83420;83421	chr2:178557037;178557036;178557035	chr2:179421764;179421763;179421762
N2A	26805	80638;80639;80640	chr2:178557037;178557036;178557035	chr2:179421764;179421763;179421762
N2B	20308	61147;61148;61149	chr2:178557037;178557036;178557035	chr2:179421764;179421763;179421762
Novex-1	20433	61522;61523;61524	chr2:178557037;178557036;178557035	chr2:179421764;179421763;179421762
Novex-2	20500	61723;61724;61725	chr2:178557037;178557036;178557035	chr2:179421764;179421763;179421762
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: Fn3-102
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1199
• 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/K	rs762557803	-1.189	0.117	D	0.439	0.415	0.251639045875	gnomAD-2.1.1	6.84E-05	None	None	None	None	N	None	0	3.47947E-04	None	9.95E-05	0	None	0	None	0	8.89E-06	4.97678E-04
E/K	rs762557803	-1.189	0.117	D	0.439	0.415	0.251639045875	gnomAD-4.0.0	2.70543E-05	None	None	None	None	N	None	0	3.20088E-04	None	4.7669E-05	0	None	0	0	0	0	6.04887E-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	0.921	likely_pathogenic	0.8851	pathogenic	-1.373	Destabilizing	0.977	D	0.636	neutral	D	0.541445628	None	None	N
E/C	0.992	likely_pathogenic	0.9894	pathogenic	-0.508	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/D	0.9135	likely_pathogenic	0.8754	pathogenic	-1.65	Destabilizing	0.977	D	0.621	neutral	N	0.506148944	None	None	N
E/F	0.9948	likely_pathogenic	0.992	pathogenic	-1.043	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/G	0.9507	likely_pathogenic	0.9229	pathogenic	-1.774	Destabilizing	0.993	D	0.755	deleterious	D	0.54980342	None	None	N
E/H	0.9845	likely_pathogenic	0.9767	pathogenic	-0.899	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/I	0.9813	likely_pathogenic	0.9742	pathogenic	-0.218	Destabilizing	0.998	D	0.822	deleterious	None	None	None	None	N
E/K	0.9535	likely_pathogenic	0.9329	pathogenic	-1.233	Destabilizing	0.117	N	0.439	neutral	D	0.524048935	None	None	N
E/L	0.9759	likely_pathogenic	0.9654	pathogenic	-0.218	Destabilizing	0.995	D	0.795	deleterious	None	None	None	None	N
E/M	0.9713	likely_pathogenic	0.9604	pathogenic	0.481	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/N	0.9863	likely_pathogenic	0.9774	pathogenic	-1.509	Destabilizing	0.995	D	0.784	deleterious	None	None	None	None	N
E/P	0.9997	likely_pathogenic	0.9996	pathogenic	-0.589	Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
E/Q	0.7164	likely_pathogenic	0.6382	pathogenic	-1.183	Destabilizing	0.977	D	0.714	prob.delet.	N	0.481573001	None	None	N
E/R	0.9702	likely_pathogenic	0.9577	pathogenic	-1.14	Destabilizing	0.99	D	0.783	deleterious	None	None	None	None	N
E/S	0.9433	likely_pathogenic	0.9137	pathogenic	-2.139	Highly Destabilizing	0.983	D	0.684	prob.neutral	None	None	None	None	N
E/T	0.9744	likely_pathogenic	0.9616	pathogenic	-1.747	Destabilizing	0.995	D	0.753	deleterious	None	None	None	None	N
E/V	0.9541	likely_pathogenic	0.9372	pathogenic	-0.589	Destabilizing	0.997	D	0.778	deleterious	D	0.530849791	None	None	N
E/W	0.9979	likely_pathogenic	0.997	pathogenic	-1.152	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/Y	0.9909	likely_pathogenic	0.9872	pathogenic	-0.846	Destabilizing	0.999	D	0.815	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.