TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3108	9547;9548;9549	chr2:178767908;178767907;178767906	chr2:179632635;179632634;179632633
N2AB	3108	9547;9548;9549	chr2:178767908;178767907;178767906	chr2:179632635;179632634;179632633
N2A	3108	9547;9548;9549	chr2:178767908;178767907;178767906	chr2:179632635;179632634;179632633
N2B	3062	9409;9410;9411	chr2:178767908;178767907;178767906	chr2:179632635;179632634;179632633
Novex-1	3062	9409;9410;9411	chr2:178767908;178767907;178767906	chr2:179632635;179632634;179632633
Novex-2	3062	9409;9410;9411	chr2:178767908;178767907;178767906	chr2:179632635;179632634;179632633
Novex-3	3108	9547;9548;9549	chr2:178767908;178767907;178767906	chr2:179632635;179632634;179632633

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-21
• Domain position: 51
• Structural Position: 130
• Q(SASA): 0.4681
• 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/D	rs756206178	-0.39	0.999	N	0.424	0.264	0.233150807113	gnomAD-2.1.1	1.06E-05	None	None	None	None	N	None	1.20163E-04	0	None	0	0	None	0	None	0	0	0
E/D	rs756206178	-0.39	0.999	N	0.424	0.264	0.233150807113	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	1.68903E-04	0	0	0	0	None	0	0	0	0	0
E/D	rs756206178	-0.39	0.999	N	0.424	0.264	0.233150807113	gnomAD-4.0.0	8.67421E-06	None	None	None	None	N	None	1.86861E-04	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	0.743	likely_pathogenic	0.7652	pathogenic	-0.683	Destabilizing	0.999	D	0.599	neutral	N	0.514811077	None	None	N
E/C	0.9943	likely_pathogenic	0.9942	pathogenic	-0.447	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/D	0.2865	likely_benign	0.3423	ambiguous	-0.762	Destabilizing	0.999	D	0.424	neutral	N	0.423860967	None	None	N
E/F	0.9842	likely_pathogenic	0.986	pathogenic	-0.257	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/G	0.6335	likely_pathogenic	0.6671	pathogenic	-0.965	Destabilizing	1.0	D	0.651	neutral	N	0.515365179	None	None	N
E/H	0.9579	likely_pathogenic	0.9577	pathogenic	-0.242	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
E/I	0.9245	likely_pathogenic	0.9307	pathogenic	0.062	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/K	0.8155	likely_pathogenic	0.8118	pathogenic	-0.36	Destabilizing	0.999	D	0.55	neutral	N	0.506106153	None	None	N
E/L	0.9281	likely_pathogenic	0.9332	pathogenic	0.062	Stabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
E/M	0.9316	likely_pathogenic	0.9407	pathogenic	0.231	Stabilizing	1.0	D	0.632	neutral	None	None	None	None	N
E/N	0.7613	likely_pathogenic	0.8048	pathogenic	-0.765	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
E/P	0.9945	likely_pathogenic	0.9941	pathogenic	-0.166	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
E/Q	0.6144	likely_pathogenic	0.6154	pathogenic	-0.682	Destabilizing	1.0	D	0.551	neutral	N	0.514640214	None	None	N
E/R	0.8892	likely_pathogenic	0.8825	pathogenic	-0.01	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
E/S	0.7669	likely_pathogenic	0.7996	pathogenic	-0.976	Destabilizing	0.999	D	0.573	neutral	None	None	None	None	N
E/T	0.8291	likely_pathogenic	0.8531	pathogenic	-0.751	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
E/V	0.8039	likely_pathogenic	0.8172	pathogenic	-0.166	Destabilizing	1.0	D	0.688	prob.neutral	D	0.547497417	None	None	N
E/W	0.9943	likely_pathogenic	0.9943	pathogenic	-0.027	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
E/Y	0.9691	likely_pathogenic	0.9708	pathogenic	-0.026	Destabilizing	1.0	D	0.663	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.