TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29590	88993;88994;88995	chr2:178554579;178554578;178554577	chr2:179419306;179419305;179419304
N2AB	27949	84070;84071;84072	chr2:178554579;178554578;178554577	chr2:179419306;179419305;179419304
N2A	27022	81289;81290;81291	chr2:178554579;178554578;178554577	chr2:179419306;179419305;179419304
N2B	20525	61798;61799;61800	chr2:178554579;178554578;178554577	chr2:179419306;179419305;179419304
Novex-1	20650	62173;62174;62175	chr2:178554579;178554578;178554577	chr2:179419306;179419305;179419304
Novex-2	20717	62374;62375;62376	chr2:178554579;178554578;178554577	chr2:179419306;179419305;179419304
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-103
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.563
• 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/D	rs879152203	-0.316	0.002	N	0.125	0.069	0.154104182512	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
E/D	rs879152203	-0.316	0.002	N	0.125	0.069	0.154104182512	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs879152203	-0.316	0.002	N	0.125	0.069	0.154104182512	gnomAD-4.0.0	1.05347E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.44086E-05	0	0
E/Q	rs72648236	-0.202	0.891	N	0.401	0.256	0.284150004643	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
E/Q	rs72648236	-0.202	0.891	N	0.401	0.256	0.284150004643	Begay (2015)	None	DCM	comp het with R14640C	None	None	N	WGS prioritisation; filtering with ANNOVAR; co-segregates within 2-generation family (n = 2, 2 affected (total 3))	None	None	None	None	None	None	None	None	None	None	None
E/Q	rs72648236	-0.202	0.891	N	0.401	0.256	0.284150004643	gnomAD-4.0.0	1.59104E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85778E-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	0.1352	likely_benign	0.1561	benign	-0.218	Destabilizing	0.454	N	0.385	neutral	N	0.432460115	None	None	N
E/C	0.8508	likely_pathogenic	0.8654	pathogenic	-0.45	Destabilizing	0.998	D	0.473	neutral	None	None	None	None	N
E/D	0.0785	likely_benign	0.0815	benign	-0.524	Destabilizing	0.002	N	0.125	neutral	N	0.372953238	None	None	N
E/F	0.8064	likely_pathogenic	0.8524	pathogenic	0.222	Stabilizing	0.991	D	0.436	neutral	None	None	None	None	N
E/G	0.1259	likely_benign	0.1498	benign	-0.46	Destabilizing	0.012	N	0.265	neutral	N	0.432558902	None	None	N
E/H	0.4541	ambiguous	0.5015	ambiguous	0.679	Stabilizing	0.991	D	0.385	neutral	None	None	None	None	N
E/I	0.5139	ambiguous	0.5723	pathogenic	0.405	Stabilizing	0.991	D	0.439	neutral	None	None	None	None	N
E/K	0.1712	likely_benign	0.1945	benign	0.134	Stabilizing	0.801	D	0.369	neutral	N	0.438906084	None	None	N
E/L	0.5108	ambiguous	0.5639	ambiguous	0.405	Stabilizing	0.974	D	0.42	neutral	None	None	None	None	N
E/M	0.5331	ambiguous	0.5872	pathogenic	0.16	Stabilizing	0.998	D	0.427	neutral	None	None	None	None	N
E/N	0.1641	likely_benign	0.1871	benign	-0.427	Destabilizing	0.842	D	0.333	neutral	None	None	None	None	N
E/P	0.7519	likely_pathogenic	0.7748	pathogenic	0.217	Stabilizing	0.991	D	0.414	neutral	None	None	None	None	N
E/Q	0.1587	likely_benign	0.1732	benign	-0.326	Destabilizing	0.891	D	0.401	neutral	N	0.434134983	None	None	N
E/R	0.3218	likely_benign	0.3551	ambiguous	0.576	Stabilizing	0.974	D	0.394	neutral	None	None	None	None	N
E/S	0.1584	likely_benign	0.1785	benign	-0.586	Destabilizing	0.842	D	0.344	neutral	None	None	None	None	N
E/T	0.1894	likely_benign	0.2193	benign	-0.371	Destabilizing	0.915	D	0.397	neutral	None	None	None	None	N
E/V	0.2942	likely_benign	0.3427	ambiguous	0.217	Stabilizing	0.966	D	0.415	neutral	N	0.424323421	None	None	N
E/W	0.9251	likely_pathogenic	0.9438	pathogenic	0.411	Stabilizing	0.998	D	0.55	neutral	None	None	None	None	N
E/Y	0.632	likely_pathogenic	0.6903	pathogenic	0.478	Stabilizing	0.991	D	0.433	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.