TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23904	71935;71936;71937	chr2:178574422;178574421;178574420	chr2:179439149;179439148;179439147
N2AB	22263	67012;67013;67014	chr2:178574422;178574421;178574420	chr2:179439149;179439148;179439147
N2A	21336	64231;64232;64233	chr2:178574422;178574421;178574420	chr2:179439149;179439148;179439147
N2B	14839	44740;44741;44742	chr2:178574422;178574421;178574420	chr2:179439149;179439148;179439147
Novex-1	14964	45115;45116;45117	chr2:178574422;178574421;178574420	chr2:179439149;179439148;179439147
Novex-2	15031	45316;45317;45318	chr2:178574422;178574421;178574420	chr2:179439149;179439148;179439147
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: Fn3-61
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2212
• Predicted PPI site: I

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	rs267599038	None	0.944	N	0.416	0.289	0.252162846088	gnomAD-4.0.0	3.18367E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71866E-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	0.4234	ambiguous	0.4904	ambiguous	-1.285	Destabilizing	0.892	D	0.505	neutral	N	0.471480462	None	None	I
E/C	0.9	likely_pathogenic	0.9235	pathogenic	-0.955	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	I
E/D	0.7529	likely_pathogenic	0.7955	pathogenic	-1.705	Destabilizing	0.981	D	0.411	neutral	N	0.50658979	None	None	I
E/F	0.9271	likely_pathogenic	0.9377	pathogenic	-1.155	Destabilizing	0.975	D	0.837	deleterious	None	None	None	None	I
E/G	0.6188	likely_pathogenic	0.6756	pathogenic	-1.671	Destabilizing	0.983	D	0.695	prob.neutral	N	0.500006424	None	None	I
E/H	0.8318	likely_pathogenic	0.848	pathogenic	-1.383	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	I
E/I	0.4515	ambiguous	0.535	ambiguous	-0.208	Destabilizing	0.95	D	0.763	deleterious	None	None	None	None	I
E/K	0.388	ambiguous	0.4373	ambiguous	-1.518	Destabilizing	0.944	D	0.416	neutral	N	0.469861074	None	None	I
E/L	0.6959	likely_pathogenic	0.7497	pathogenic	-0.208	Destabilizing	0.033	N	0.517	neutral	None	None	None	None	I
E/M	0.5889	likely_pathogenic	0.6632	pathogenic	0.426	Stabilizing	0.993	D	0.803	deleterious	None	None	None	None	I
E/N	0.7743	likely_pathogenic	0.8272	pathogenic	-1.765	Destabilizing	0.996	D	0.64	neutral	None	None	None	None	I
E/P	0.9974	likely_pathogenic	0.998	pathogenic	-0.549	Destabilizing	0.996	D	0.775	deleterious	None	None	None	None	I
E/Q	0.1994	likely_benign	0.2029	benign	-1.532	Destabilizing	0.994	D	0.577	neutral	N	0.51613193	None	None	I
E/R	0.5999	likely_pathogenic	0.6184	pathogenic	-1.367	Destabilizing	0.987	D	0.637	neutral	None	None	None	None	I
E/S	0.5615	ambiguous	0.6288	pathogenic	-2.323	Highly Destabilizing	0.957	D	0.432	neutral	None	None	None	None	I
E/T	0.5466	ambiguous	0.6277	pathogenic	-1.978	Destabilizing	0.975	D	0.688	prob.neutral	None	None	None	None	I
E/V	0.266	likely_benign	0.3245	benign	-0.549	Destabilizing	0.805	D	0.617	neutral	N	0.456923337	None	None	I
E/W	0.9826	likely_pathogenic	0.9831	pathogenic	-1.229	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	I
E/Y	0.906	likely_pathogenic	0.9152	pathogenic	-0.993	Destabilizing	0.987	D	0.821	deleterious	None	None	None	None	I

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.