TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6771	20536;20537;20538	chr2:178726011;178726010;178726009	chr2:179590738;179590737;179590736
N2AB	6454	19585;19586;19587	chr2:178726011;178726010;178726009	chr2:179590738;179590737;179590736
N2A	5527	16804;16805;16806	chr2:178726011;178726010;178726009	chr2:179590738;179590737;179590736
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-52
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.6468
• 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/Q	rs750614578	0.023	0.385	N	0.472	0.257	0.272639205421	gnomAD-2.1.1	8.75E-06	None	None	None	None	N	None	0	0	None	1.11185E-04	0	None	0	None	0	9.46E-06	0
E/Q	rs750614578	0.023	0.385	N	0.472	0.257	0.272639205421	gnomAD-4.0.0	2.81713E-06	None	None	None	None	N	None	0	0	None	1.20715E-04	0	None	0	0	9.18771E-07	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	0.1832	likely_benign	0.1729	benign	-0.525	Destabilizing	0.321	N	0.552	neutral	N	0.488303357	None	None	N
E/C	0.8747	likely_pathogenic	0.876	pathogenic	-0.242	Destabilizing	0.981	D	0.728	prob.delet.	None	None	None	None	N
E/D	0.1206	likely_benign	0.1044	benign	-0.549	Destabilizing	None	N	0.164	neutral	D	0.535003771	None	None	N
E/F	0.7811	likely_pathogenic	0.7605	pathogenic	-0.211	Destabilizing	0.962	D	0.651	neutral	None	None	None	None	N
E/G	0.1772	likely_benign	0.1751	benign	-0.77	Destabilizing	0.611	D	0.545	neutral	D	0.530136669	None	None	N
E/H	0.4943	ambiguous	0.4684	ambiguous	-0.034	Destabilizing	0.947	D	0.491	neutral	None	None	None	None	N
E/I	0.4865	ambiguous	0.4473	ambiguous	0.103	Stabilizing	0.794	D	0.639	neutral	None	None	None	None	N
E/K	0.2202	likely_benign	0.2091	benign	0.079	Stabilizing	0.466	N	0.531	neutral	D	0.524997421	None	None	N
E/L	0.4744	ambiguous	0.4364	ambiguous	0.103	Stabilizing	0.794	D	0.625	neutral	None	None	None	None	N
E/M	0.5684	likely_pathogenic	0.5312	ambiguous	0.199	Stabilizing	0.888	D	0.619	neutral	None	None	None	None	N
E/N	0.2445	likely_benign	0.2152	benign	-0.349	Destabilizing	0.112	N	0.491	neutral	None	None	None	None	N
E/P	0.5025	ambiguous	0.4965	ambiguous	-0.086	Destabilizing	0.365	N	0.539	neutral	None	None	None	None	N
E/Q	0.1752	likely_benign	0.1588	benign	-0.292	Destabilizing	0.385	N	0.472	neutral	N	0.513647064	None	None	N
E/R	0.3655	ambiguous	0.3503	ambiguous	0.382	Stabilizing	0.803	D	0.497	neutral	None	None	None	None	N
E/S	0.2109	likely_benign	0.1939	benign	-0.525	Destabilizing	0.238	N	0.505	neutral	None	None	None	None	N
E/T	0.2573	likely_benign	0.2314	benign	-0.325	Destabilizing	0.463	N	0.529	neutral	None	None	None	None	N
E/V	0.2773	likely_benign	0.256	benign	-0.086	Destabilizing	0.674	D	0.558	neutral	N	0.518108734	None	None	N
E/W	0.9061	likely_pathogenic	0.9008	pathogenic	0.006	Stabilizing	0.996	D	0.741	deleterious	None	None	None	None	N
E/Y	0.6188	likely_pathogenic	0.5997	pathogenic	0.043	Stabilizing	0.985	D	0.625	neutral	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.