TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8869	26830;26831;26832	chr2:178714053;178714052;178714051	chr2:179578780;179578779;179578778
N2AB	8552	25879;25880;25881	chr2:178714053;178714052;178714051	chr2:179578780;179578779;179578778
N2A	7625	23098;23099;23100	chr2:178714053;178714052;178714051	chr2:179578780;179578779;179578778
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: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-74
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.4428
• 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	rs375373507	0.198	0.698	N	0.549	0.159	None	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.45E-05	0
E/K	rs375373507	0.198	0.698	N	0.549	0.159	None	gnomAD-4.0.0	5.47442E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29675E-06	0	1.65706E-05

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	0.1147	likely_benign	0.1316	benign	-0.559	Destabilizing	0.698	D	0.581	neutral	D	0.535137057	None	None	N
E/C	0.7794	likely_pathogenic	0.833	pathogenic	-0.411	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
E/D	0.2712	likely_benign	0.3554	ambiguous	-0.659	Destabilizing	0.822	D	0.489	neutral	N	0.518916811	None	None	N
E/F	0.6538	likely_pathogenic	0.7615	pathogenic	0.1	Stabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
E/G	0.2012	likely_benign	0.2556	benign	-0.869	Destabilizing	0.942	D	0.6	neutral	N	0.499939605	None	None	N
E/H	0.4903	ambiguous	0.5859	pathogenic	0.289	Stabilizing	0.994	D	0.656	neutral	None	None	None	None	N
E/I	0.1764	likely_benign	0.2398	benign	0.269	Stabilizing	0.978	D	0.759	deleterious	None	None	None	None	N
E/K	0.1386	likely_benign	0.1608	benign	-0.08	Destabilizing	0.698	D	0.549	neutral	N	0.495578591	None	None	N
E/L	0.205	likely_benign	0.2718	benign	0.269	Stabilizing	0.956	D	0.679	prob.neutral	None	None	None	None	N
E/M	0.2565	likely_benign	0.3222	benign	0.326	Stabilizing	0.994	D	0.706	prob.neutral	None	None	None	None	N
E/N	0.3509	ambiguous	0.4345	ambiguous	-0.729	Destabilizing	0.956	D	0.642	neutral	None	None	None	None	N
E/P	0.2463	likely_benign	0.2852	benign	0.014	Stabilizing	0.978	D	0.735	prob.delet.	None	None	None	None	N
E/Q	0.1201	likely_benign	0.1373	benign	-0.599	Destabilizing	0.058	N	0.297	neutral	D	0.52769101	None	None	N
E/R	0.2339	likely_benign	0.2938	benign	0.345	Stabilizing	0.915	D	0.627	neutral	None	None	None	None	N
E/S	0.2526	likely_benign	0.3148	benign	-0.926	Destabilizing	0.754	D	0.584	neutral	None	None	None	None	N
E/T	0.2185	likely_benign	0.2734	benign	-0.658	Destabilizing	0.956	D	0.664	neutral	None	None	None	None	N
E/V	0.1136	likely_benign	0.1462	benign	0.014	Stabilizing	0.942	D	0.684	prob.neutral	D	0.528557801	None	None	N
E/W	0.8585	likely_pathogenic	0.9179	pathogenic	0.396	Stabilizing	0.998	D	0.748	deleterious	None	None	None	None	N
E/Y	0.5425	ambiguous	0.6496	pathogenic	0.376	Stabilizing	0.978	D	0.726	prob.delet.	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.