TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19029	57310;57311;57312	chr2:178598532;178598531;178598530	chr2:179463259;179463258;179463257
N2AB	17388	52387;52388;52389	chr2:178598532;178598531;178598530	chr2:179463259;179463258;179463257
N2A	16461	49606;49607;49608	chr2:178598532;178598531;178598530	chr2:179463259;179463258;179463257
N2B	9964	30115;30116;30117	chr2:178598532;178598531;178598530	chr2:179463259;179463258;179463257
Novex-1	10089	30490;30491;30492	chr2:178598532;178598531;178598530	chr2:179463259;179463258;179463257
Novex-2	10156	30691;30692;30693	chr2:178598532;178598531;178598530	chr2:179463259;179463258;179463257
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: Fn3-26
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.3587
• 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	None	None	0.698	N	0.438	0.244	0.251639045875	gnomAD-4.0.0	1.37312E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00409E-07	1.18223E-05	0
E/Q	rs761979702	-0.785	0.294	N	0.227	0.116	0.195762928549	gnomAD-2.1.1	1.64E-05	None	None	None	None	N	None	0	0	None	0	2.29043E-04	None	0	None	0	0	0
E/Q	rs761979702	-0.785	0.294	N	0.227	0.116	0.195762928549	gnomAD-4.0.0	1.51043E-05	None	None	None	None	N	None	0	0	None	0	5.5747E-04	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	0.1422	likely_benign	0.1515	benign	-0.622	Destabilizing	0.822	D	0.521	neutral	N	0.521695252	None	None	N
E/C	0.8505	likely_pathogenic	0.8595	pathogenic	-0.379	Destabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	N
E/D	0.3765	ambiguous	0.3881	ambiguous	-0.967	Destabilizing	0.014	N	0.274	neutral	N	0.485697167	None	None	N
E/F	0.8656	likely_pathogenic	0.8836	pathogenic	0.189	Stabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
E/G	0.3149	likely_benign	0.2911	benign	-1.003	Destabilizing	0.822	D	0.587	neutral	D	0.524004839	None	None	N
E/H	0.7478	likely_pathogenic	0.7565	pathogenic	0.103	Stabilizing	0.994	D	0.614	neutral	None	None	None	None	N
E/I	0.2774	likely_benign	0.3234	benign	0.422	Stabilizing	0.978	D	0.79	deleterious	None	None	None	None	N
E/K	0.2064	likely_benign	0.2046	benign	-0.31	Destabilizing	0.698	D	0.438	neutral	N	0.473613304	None	None	N
E/L	0.2843	likely_benign	0.3138	benign	0.422	Stabilizing	0.956	D	0.761	deleterious	None	None	None	None	N
E/M	0.3644	ambiguous	0.3861	ambiguous	0.687	Stabilizing	0.998	D	0.708	prob.delet.	None	None	None	None	N
E/N	0.5326	ambiguous	0.5433	ambiguous	-0.97	Destabilizing	0.915	D	0.575	neutral	None	None	None	None	N
E/P	0.4807	ambiguous	0.5065	ambiguous	0.096	Stabilizing	0.978	D	0.75	deleterious	None	None	None	None	N
E/Q	0.1796	likely_benign	0.1839	benign	-0.806	Destabilizing	0.294	N	0.227	neutral	N	0.48384894	None	None	N
E/R	0.3759	ambiguous	0.3737	ambiguous	0.072	Stabilizing	0.956	D	0.586	neutral	None	None	None	None	N
E/S	0.4041	ambiguous	0.4136	ambiguous	-1.248	Destabilizing	0.86	D	0.484	neutral	None	None	None	None	N
E/T	0.3194	likely_benign	0.3336	benign	-0.92	Destabilizing	0.956	D	0.649	neutral	None	None	None	None	N
E/V	0.1562	likely_benign	0.1775	benign	0.096	Stabilizing	0.971	D	0.731	prob.delet.	N	0.471118976	None	None	N
E/W	0.9499	likely_pathogenic	0.9558	pathogenic	0.505	Stabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
E/Y	0.8096	likely_pathogenic	0.8249	pathogenic	0.478	Stabilizing	0.993	D	0.753	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.