TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21408	64447;64448;64449	chr2:178586679;178586678;178586677	chr2:179451406;179451405;179451404
N2AB	19767	59524;59525;59526	chr2:178586679;178586678;178586677	chr2:179451406;179451405;179451404
N2A	18840	56743;56744;56745	chr2:178586679;178586678;178586677	chr2:179451406;179451405;179451404
N2B	12343	37252;37253;37254	chr2:178586679;178586678;178586677	chr2:179451406;179451405;179451404
Novex-1	12468	37627;37628;37629	chr2:178586679;178586678;178586677	chr2:179451406;179451405;179451404
Novex-2	12535	37828;37829;37830	chr2:178586679;178586678;178586677	chr2:179451406;179451405;179451404
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: Fn3-43
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.2581
• 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	0.896	N	0.53	0.231	0.28058544554	gnomAD-4.0.0	1.59261E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86102E-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	0.1442	likely_benign	0.1324	benign	-0.633	Destabilizing	0.896	D	0.514	neutral	N	0.465551181	None	None	N
E/C	0.9076	likely_pathogenic	0.8757	pathogenic	-0.418	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
E/D	0.1348	likely_benign	0.132	benign	-0.876	Destabilizing	0.011	N	0.165	neutral	N	0.466167256	None	None	N
E/F	0.8389	likely_pathogenic	0.7854	pathogenic	-0.208	Destabilizing	0.988	D	0.729	prob.delet.	None	None	None	None	N
E/G	0.215	likely_benign	0.1843	benign	-0.943	Destabilizing	0.896	D	0.62	neutral	N	0.466572688	None	None	N
E/H	0.7432	likely_pathogenic	0.6731	pathogenic	-0.38	Destabilizing	0.159	N	0.331	neutral	None	None	None	None	N
E/I	0.3728	ambiguous	0.3233	benign	0.193	Stabilizing	0.988	D	0.732	prob.delet.	None	None	None	None	N
E/K	0.3953	ambiguous	0.3212	benign	-0.475	Destabilizing	0.896	D	0.53	neutral	N	0.450851087	None	None	N
E/L	0.4389	ambiguous	0.3825	ambiguous	0.193	Stabilizing	0.976	D	0.729	prob.delet.	None	None	None	None	N
E/M	0.495	ambiguous	0.4415	ambiguous	0.414	Stabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
E/N	0.3703	ambiguous	0.3229	benign	-0.826	Destabilizing	0.851	D	0.504	neutral	None	None	None	None	N
E/P	0.6096	likely_pathogenic	0.5683	pathogenic	-0.061	Destabilizing	0.988	D	0.586	neutral	None	None	None	None	N
E/Q	0.3028	likely_benign	0.2547	benign	-0.724	Destabilizing	0.968	D	0.52	neutral	N	0.504589572	None	None	N
E/R	0.5987	likely_pathogenic	0.5156	ambiguous	-0.181	Destabilizing	0.976	D	0.549	neutral	None	None	None	None	N
E/S	0.2544	likely_benign	0.2255	benign	-1.067	Destabilizing	0.919	D	0.5	neutral	None	None	None	None	N
E/T	0.2658	likely_benign	0.2323	benign	-0.822	Destabilizing	0.988	D	0.509	neutral	None	None	None	None	N
E/V	0.226	likely_benign	0.2023	benign	-0.061	Destabilizing	0.984	D	0.693	prob.neutral	N	0.445098551	None	None	N
E/W	0.9407	likely_pathogenic	0.9144	pathogenic	-0.012	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
E/Y	0.7555	likely_pathogenic	0.6906	pathogenic	0.014	Stabilizing	0.976	D	0.701	prob.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.