TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32380	97363;97364;97365	chr2:178542716;178542715;178542714	chr2:179407443;179407442;179407441
N2AB	30739	92440;92441;92442	chr2:178542716;178542715;178542714	chr2:179407443;179407442;179407441
N2A	29812	89659;89660;89661	chr2:178542716;178542715;178542714	chr2:179407443;179407442;179407441
N2B	23315	70168;70169;70170	chr2:178542716;178542715;178542714	chr2:179407443;179407442;179407441
Novex-1	23440	70543;70544;70545	chr2:178542716;178542715;178542714	chr2:179407443;179407442;179407441
Novex-2	23507	70744;70745;70746	chr2:178542716;178542715;178542714	chr2:179407443;179407442;179407441
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: Ig-154
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.2656
• 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/A	None	None	0.996	N	0.665	0.536	0.45553875121	gnomAD-4.0.0	3.42106E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49742E-06	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	0.2553	likely_benign	0.1938	benign	-1.218	Destabilizing	0.996	D	0.665	neutral	N	0.515319145	None	None	N
E/C	0.8519	likely_pathogenic	0.7897	pathogenic	-0.545	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/D	0.3953	ambiguous	0.3308	benign	-1.07	Destabilizing	0.962	D	0.517	neutral	N	0.485403295	None	None	N
E/F	0.8234	likely_pathogenic	0.7504	pathogenic	-0.665	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/G	0.4624	ambiguous	0.3587	ambiguous	-1.597	Destabilizing	0.992	D	0.721	prob.delet.	N	0.497431163	None	None	N
E/H	0.5782	likely_pathogenic	0.458	ambiguous	-0.876	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
E/I	0.3543	ambiguous	0.3016	benign	-0.162	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
E/K	0.384	ambiguous	0.2828	benign	-0.5	Destabilizing	0.992	D	0.585	neutral	N	0.472200299	None	None	N
E/L	0.4208	ambiguous	0.3429	ambiguous	-0.162	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
E/M	0.4669	ambiguous	0.3981	ambiguous	0.415	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/N	0.5174	ambiguous	0.4282	ambiguous	-1.022	Destabilizing	0.833	D	0.33	neutral	None	None	None	None	N
E/P	0.9899	likely_pathogenic	0.9817	pathogenic	-0.495	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/Q	0.1607	likely_benign	0.1229	benign	-0.889	Destabilizing	0.999	D	0.694	prob.neutral	N	0.508910461	None	None	N
E/R	0.4985	ambiguous	0.3824	ambiguous	-0.326	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
E/S	0.3405	ambiguous	0.2684	benign	-1.449	Destabilizing	0.994	D	0.582	neutral	None	None	None	None	N
E/T	0.2749	likely_benign	0.2183	benign	-1.101	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
E/V	0.2193	likely_benign	0.1857	benign	-0.495	Destabilizing	1.0	D	0.817	deleterious	N	0.432663263	None	None	N
E/W	0.9554	likely_pathogenic	0.9233	pathogenic	-0.333	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Y	0.7624	likely_pathogenic	0.6677	pathogenic	-0.345	Destabilizing	1.0	D	0.839	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.