TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29179	87760;87761;87762	chr2:178557819;178557818;178557817	chr2:179422546;179422545;179422544
N2AB	27538	82837;82838;82839	chr2:178557819;178557818;178557817	chr2:179422546;179422545;179422544
N2A	26611	80056;80057;80058	chr2:178557819;178557818;178557817	chr2:179422546;179422545;179422544
N2B	20114	60565;60566;60567	chr2:178557819;178557818;178557817	chr2:179422546;179422545;179422544
Novex-1	20239	60940;60941;60942	chr2:178557819;178557818;178557817	chr2:179422546;179422545;179422544
Novex-2	20306	61141;61142;61143	chr2:178557819;178557818;178557817	chr2:179422546;179422545;179422544
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: Fn3-100
• Domain position: 43
• Structural Position: 44
• Q(SASA): 0.2116
• 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	0.999	N	0.629	0.568	0.384584525793	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
E/D	None	None	0.999	N	0.463	0.193	0.272205846399	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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	0.2653	likely_benign	0.3026	benign	-0.945	Destabilizing	0.999	D	0.629	neutral	N	0.478827977	None	None	N
E/C	0.915	likely_pathogenic	0.9308	pathogenic	-0.431	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
E/D	0.1936	likely_benign	0.201	benign	-1.148	Destabilizing	0.999	D	0.463	neutral	N	0.406236305	None	None	N
E/F	0.9486	likely_pathogenic	0.9566	pathogenic	-0.566	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/G	0.3394	likely_benign	0.357	ambiguous	-1.289	Destabilizing	1.0	D	0.663	neutral	N	0.483133618	None	None	N
E/H	0.7715	likely_pathogenic	0.8045	pathogenic	-0.86	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
E/I	0.6895	likely_pathogenic	0.75	pathogenic	-0.012	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/K	0.3457	ambiguous	0.3943	ambiguous	-0.556	Destabilizing	0.999	D	0.549	neutral	N	0.484926376	None	None	N
E/L	0.6422	likely_pathogenic	0.6946	pathogenic	-0.012	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/M	0.6804	likely_pathogenic	0.7224	pathogenic	0.515	Stabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
E/N	0.4201	ambiguous	0.4548	ambiguous	-1.0	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/P	0.6324	likely_pathogenic	0.7271	pathogenic	-0.302	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/Q	0.2506	likely_benign	0.2769	benign	-0.893	Destabilizing	1.0	D	0.599	neutral	N	0.521020462	None	None	N
E/R	0.5725	likely_pathogenic	0.6199	pathogenic	-0.349	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/S	0.4057	ambiguous	0.446	ambiguous	-1.299	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
E/T	0.5052	ambiguous	0.5663	pathogenic	-1.009	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/V	0.4494	ambiguous	0.5156	ambiguous	-0.302	Destabilizing	1.0	D	0.765	deleterious	N	0.485108628	None	None	N
E/W	0.9832	likely_pathogenic	0.9848	pathogenic	-0.332	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/Y	0.9126	likely_pathogenic	0.9254	pathogenic	-0.312	Destabilizing	1.0	D	0.745	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.