TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34330	103213;103214;103215	chr2:178533627;178533626;178533625	chr2:179398354;179398353;179398352
N2AB	32689	98290;98291;98292	chr2:178533627;178533626;178533625	chr2:179398354;179398353;179398352
N2A	31762	95509;95510;95511	chr2:178533627;178533626;178533625	chr2:179398354;179398353;179398352
N2B	25265	76018;76019;76020	chr2:178533627;178533626;178533625	chr2:179398354;179398353;179398352
Novex-1	25390	76393;76394;76395	chr2:178533627;178533626;178533625	chr2:179398354;179398353;179398352
Novex-2	25457	76594;76595;76596	chr2:178533627;178533626;178533625	chr2:179398354;179398353;179398352
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-161
• Domain position: 73
• Structural Position: 153
• Q(SASA): 0.5227
• 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	0.969	N	0.575	0.361	0.421427970867	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.275	likely_benign	0.3405	ambiguous	-0.829	Destabilizing	0.939	D	0.623	neutral	D	0.531019317	None	None	N
E/C	0.943	likely_pathogenic	0.96	pathogenic	-0.268	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
E/D	0.24	likely_benign	0.2859	benign	-0.999	Destabilizing	0.99	D	0.513	neutral	N	0.487631794	None	None	N
E/F	0.8702	likely_pathogenic	0.9094	pathogenic	-0.729	Destabilizing	0.986	D	0.794	deleterious	None	None	None	None	N
E/G	0.4981	ambiguous	0.5897	pathogenic	-1.127	Destabilizing	0.997	D	0.743	deleterious	D	0.535223063	None	None	N
E/H	0.7709	likely_pathogenic	0.8343	pathogenic	-1.009	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
E/I	0.4196	ambiguous	0.4835	ambiguous	-0.039	Destabilizing	0.128	N	0.493	neutral	None	None	None	None	N
E/K	0.3812	ambiguous	0.473	ambiguous	-0.326	Destabilizing	0.969	D	0.575	neutral	N	0.498040106	None	None	N
E/L	0.555	ambiguous	0.6165	pathogenic	-0.039	Destabilizing	0.91	D	0.66	neutral	None	None	None	None	N
E/M	0.6034	likely_pathogenic	0.662	pathogenic	0.457	Stabilizing	0.996	D	0.776	deleterious	None	None	None	None	N
E/N	0.4554	ambiguous	0.5529	ambiguous	-0.656	Destabilizing	0.998	D	0.686	prob.neutral	None	None	None	None	N
E/P	0.8061	likely_pathogenic	0.8246	pathogenic	-0.282	Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
E/Q	0.3101	likely_benign	0.3684	ambiguous	-0.603	Destabilizing	0.997	D	0.645	neutral	N	0.520879681	None	None	N
E/R	0.5939	likely_pathogenic	0.6715	pathogenic	-0.23	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	N
E/S	0.3591	ambiguous	0.447	ambiguous	-0.934	Destabilizing	0.976	D	0.591	neutral	None	None	None	None	N
E/T	0.2864	likely_benign	0.3538	ambiguous	-0.688	Destabilizing	0.986	D	0.75	deleterious	None	None	None	None	N
E/V	0.266	likely_benign	0.3292	benign	-0.282	Destabilizing	0.885	D	0.625	neutral	N	0.481804005	None	None	N
E/W	0.9605	likely_pathogenic	0.9746	pathogenic	-0.574	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
E/Y	0.8226	likely_pathogenic	0.8763	pathogenic	-0.483	Destabilizing	0.998	D	0.782	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.