TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15018	45277;45278;45279	chr2:178621870;178621869;178621868	chr2:179486597;179486596;179486595
N2AB	13377	40354;40355;40356	chr2:178621870;178621869;178621868	chr2:179486597;179486596;179486595
N2A	12450	37573;37574;37575	chr2:178621870;178621869;178621868	chr2:179486597;179486596;179486595
N2B	5953	18082;18083;18084	chr2:178621870;178621869;178621868	chr2:179486597;179486596;179486595
Novex-1	6078	18457;18458;18459	chr2:178621870;178621869;178621868	chr2:179486597;179486596;179486595
Novex-2	6145	18658;18659;18660	chr2:178621870;178621869;178621868	chr2:179486597;179486596;179486595
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCG
• RefSeq wild type template codon: CGC
• Domain: Ig-101
• Domain position: 77
• Structural Position: 162
• Q(SASA): 0.1173
• 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
A/E	rs72677221	-1.039	0.991	N	0.607	0.334	0.413241256734	gnomAD-2.1.1	1.21904E-04	None	None	None	None	N	None	0	7.39645E-04	None	0	0	None	0	None	4.01E-05	5.49E-05	0
A/E	rs72677221	-1.039	0.991	N	0.607	0.334	0.413241256734	gnomAD-3.1.2	1.98E-05	None	None	None	None	N	None	0	1.97135E-04	0	0	0	None	0	0	0	0	0
A/E	rs72677221	-1.039	0.991	N	0.607	0.334	0.413241256734	gnomAD-4.0.0	3.22591E-05	None	None	None	None	N	None	0	5.35117E-04	None	0	0	None	4.69307E-05	0	1.35713E-05	0	1.60344E-05
A/G	None	None	0.979	N	0.518	0.269	0.34854441366	gnomAD-4.0.0	6.84892E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00059E-07	0	0
A/V	rs72677221	-0.305	0.998	N	0.563	0.22	None	gnomAD-2.1.1	7.74449E-04	None	None	None	None	N	None	4.14E-05	5.66113E-03	None	0	0	None	0	None	0	7.85E-05	8.46501E-04
A/V	rs72677221	-0.305	0.998	N	0.563	0.22	None	gnomAD-3.1.2	4.08255E-04	None	None	None	None	N	None	7.25E-05	3.67985E-03	0	0	1.95084E-04	None	0	0	2.94E-05	0	0
A/V	rs72677221	-0.305	0.998	N	0.563	0.22	None	1000 genomes	1.79712E-03	None	None	None	None	N	None	0	1.15E-02	None	None	1E-03	0	None	None	None	0	None
A/V	rs72677221	-0.305	0.998	N	0.563	0.22	None	gnomAD-4.0.0	2.25177E-04	None	None	None	None	N	None	5.33974E-05	4.9985E-03	None	0	8.97344E-05	None	0	0	3.30802E-05	2.19775E-05	2.40431E-04

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
A/C	0.6079	likely_pathogenic	0.6082	pathogenic	-0.571	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
A/D	0.4689	ambiguous	0.4943	ambiguous	-0.671	Destabilizing	0.995	D	0.623	neutral	None	None	None	None	N
A/E	0.3785	ambiguous	0.4076	ambiguous	-0.715	Destabilizing	0.991	D	0.607	neutral	N	0.455868797	None	None	N
A/F	0.5031	ambiguous	0.5393	ambiguous	-0.78	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
A/G	0.1907	likely_benign	0.2105	benign	-0.852	Destabilizing	0.979	D	0.518	neutral	N	0.453745352	None	None	N
A/H	0.6186	likely_pathogenic	0.662	pathogenic	-1.05	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
A/I	0.4548	ambiguous	0.4674	ambiguous	-0.154	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	N
A/K	0.6327	likely_pathogenic	0.6594	pathogenic	-0.903	Destabilizing	0.983	D	0.619	neutral	None	None	None	None	N
A/L	0.3253	likely_benign	0.3636	ambiguous	-0.154	Destabilizing	0.992	D	0.587	neutral	None	None	None	None	N
A/M	0.3831	ambiguous	0.4015	ambiguous	-0.17	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
A/N	0.4074	ambiguous	0.4464	ambiguous	-0.584	Destabilizing	0.995	D	0.632	neutral	None	None	None	None	N
A/P	0.8293	likely_pathogenic	0.8858	pathogenic	-0.268	Destabilizing	0.997	D	0.685	prob.neutral	N	0.492466166	None	None	N
A/Q	0.4225	ambiguous	0.4596	ambiguous	-0.727	Destabilizing	0.998	D	0.705	prob.neutral	None	None	None	None	N
A/R	0.5426	ambiguous	0.5801	pathogenic	-0.608	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
A/S	0.0959	likely_benign	0.1001	benign	-0.907	Destabilizing	0.418	N	0.28	neutral	N	0.422225019	None	None	N
A/T	0.125	likely_benign	0.129	benign	-0.855	Destabilizing	0.956	D	0.52	neutral	N	0.472362325	None	None	N
A/V	0.222	likely_benign	0.2353	benign	-0.268	Destabilizing	0.998	D	0.563	neutral	N	0.434229665	None	None	N
A/W	0.8528	likely_pathogenic	0.8889	pathogenic	-1.131	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
A/Y	0.6522	likely_pathogenic	0.6958	pathogenic	-0.7	Destabilizing	0.999	D	0.679	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.