TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18333	55222;55223;55224	chr2:178602405;178602404;178602403	chr2:179467132;179467131;179467130
N2AB	16692	50299;50300;50301	chr2:178602405;178602404;178602403	chr2:179467132;179467131;179467130
N2A	15765	47518;47519;47520	chr2:178602405;178602404;178602403	chr2:179467132;179467131;179467130
N2B	9268	28027;28028;28029	chr2:178602405;178602404;178602403	chr2:179467132;179467131;179467130
Novex-1	9393	28402;28403;28404	chr2:178602405;178602404;178602403	chr2:179467132;179467131;179467130
Novex-2	9460	28603;28604;28605	chr2:178602405;178602404;178602403	chr2:179467132;179467131;179467130
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: Fn3-21
• Domain position: 62
• Structural Position: 90
• Q(SASA): 0.2921
• 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	rs764950995	-0.988	0.961	N	0.413	0.202	0.266843984389	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/D	rs764950995	-0.988	0.961	N	0.413	0.202	0.266843984389	gnomAD-3.1.2	4.61E-05	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	8.83E-05	0	0
E/D	rs764950995	-0.988	0.961	N	0.413	0.202	0.266843984389	gnomAD-4.0.0	6.13903E-05	None	None	None	None	N	None	1.3364E-05	0	None	0	0	None	0	0	8.31051E-05	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	0.1662	likely_benign	0.1777	benign	-0.874	Destabilizing	0.835	D	0.48	neutral	N	0.509360673	None	None	N
E/C	0.7659	likely_pathogenic	0.7991	pathogenic	-0.444	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
E/D	0.1375	likely_benign	0.1482	benign	-0.758	Destabilizing	0.961	D	0.413	neutral	N	0.484650874	None	None	N
E/F	0.6906	likely_pathogenic	0.7217	pathogenic	-0.307	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	N
E/G	0.2254	likely_benign	0.2468	benign	-1.182	Destabilizing	0.961	D	0.559	neutral	N	0.471306332	None	None	N
E/H	0.3777	ambiguous	0.3694	ambiguous	-0.265	Destabilizing	1.0	D	0.537	neutral	None	None	None	None	N
E/I	0.3513	ambiguous	0.3537	ambiguous	-0.049	Destabilizing	0.983	D	0.646	neutral	None	None	None	None	N
E/K	0.1781	likely_benign	0.1744	benign	-0.345	Destabilizing	0.961	D	0.387	neutral	N	0.471727792	None	None	N
E/L	0.4474	ambiguous	0.4411	ambiguous	-0.049	Destabilizing	0.942	D	0.583	neutral	None	None	None	None	N
E/M	0.4613	ambiguous	0.4829	ambiguous	0.225	Stabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	N
E/N	0.2325	likely_benign	0.2476	benign	-0.824	Destabilizing	0.991	D	0.513	neutral	None	None	None	None	N
E/P	0.9225	likely_pathogenic	0.9275	pathogenic	-0.304	Destabilizing	0.996	D	0.657	neutral	None	None	None	None	N
E/Q	0.1348	likely_benign	0.1233	benign	-0.727	Destabilizing	0.994	D	0.539	neutral	N	0.504512214	None	None	N
E/R	0.2892	likely_benign	0.2848	benign	0.047	Stabilizing	0.996	D	0.527	neutral	None	None	None	None	N
E/S	0.1685	likely_benign	0.1719	benign	-1.072	Destabilizing	0.559	D	0.438	neutral	None	None	None	None	N
E/T	0.1819	likely_benign	0.1823	benign	-0.817	Destabilizing	0.942	D	0.503	neutral	None	None	None	None	N
E/V	0.2226	likely_benign	0.2189	benign	-0.304	Destabilizing	0.433	N	0.439	neutral	N	0.517230795	None	None	N
E/W	0.8778	likely_pathogenic	0.8931	pathogenic	0.01	Stabilizing	1.0	D	0.638	neutral	None	None	None	None	N
E/Y	0.5692	likely_pathogenic	0.5957	pathogenic	-0.04	Destabilizing	0.999	D	0.719	prob.delet.	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.