TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22397	67414;67415;67416	chr2:178580098;178580097;178580096	chr2:179444825;179444824;179444823
N2AB	20756	62491;62492;62493	chr2:178580098;178580097;178580096	chr2:179444825;179444824;179444823
N2A	19829	59710;59711;59712	chr2:178580098;178580097;178580096	chr2:179444825;179444824;179444823
N2B	13332	40219;40220;40221	chr2:178580098;178580097;178580096	chr2:179444825;179444824;179444823
Novex-1	13457	40594;40595;40596	chr2:178580098;178580097;178580096	chr2:179444825;179444824;179444823
Novex-2	13524	40795;40796;40797	chr2:178580098;178580097;178580096	chr2:179444825;179444824;179444823
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: Fn3-50
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.644
• 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/A	None	None	0.999	N	0.571	0.418	0.373897652646	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/G	None	None	1.0	N	0.587	0.395	0.360565625551	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-06	0	0
E/K	rs1163846592	None	0.999	N	0.584	0.411	0.350524144436	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs1163846592	None	0.999	N	0.584	0.411	0.350524144436	gnomAD-4.0.0	6.81847E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.32597E-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	0.2416	likely_benign	0.2617	benign	-0.135	Destabilizing	0.999	D	0.571	neutral	N	0.444869264	None	None	N
E/C	0.9255	likely_pathogenic	0.9242	pathogenic	-0.117	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/D	0.1553	likely_benign	0.1564	benign	-0.245	Destabilizing	0.999	D	0.439	neutral	N	0.419546745	None	None	N
E/F	0.8921	likely_pathogenic	0.9	pathogenic	-0.134	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
E/G	0.211	likely_benign	0.2282	benign	-0.27	Destabilizing	1.0	D	0.587	neutral	N	0.420122749	None	None	N
E/H	0.6958	likely_pathogenic	0.7063	pathogenic	0.386	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	N
E/I	0.6765	likely_pathogenic	0.6794	pathogenic	0.169	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/K	0.3426	ambiguous	0.3728	ambiguous	0.413	Stabilizing	0.999	D	0.584	neutral	N	0.446773419	None	None	N
E/L	0.5577	ambiguous	0.5699	pathogenic	0.169	Stabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
E/M	0.6782	likely_pathogenic	0.6883	pathogenic	0.043	Stabilizing	1.0	D	0.637	neutral	None	None	None	None	N
E/N	0.4009	ambiguous	0.4147	ambiguous	0.182	Stabilizing	1.0	D	0.615	neutral	None	None	None	None	N
E/P	0.8598	likely_pathogenic	0.8746	pathogenic	0.086	Stabilizing	1.0	D	0.593	neutral	None	None	None	None	N
E/Q	0.2285	likely_benign	0.2425	benign	0.191	Stabilizing	1.0	D	0.513	neutral	N	0.490236195	None	None	N
E/R	0.468	ambiguous	0.5014	ambiguous	0.647	Stabilizing	1.0	D	0.613	neutral	None	None	None	None	N
E/S	0.2742	likely_benign	0.278	benign	0.02	Stabilizing	0.999	D	0.557	neutral	None	None	None	None	N
E/T	0.3277	likely_benign	0.3366	benign	0.135	Stabilizing	1.0	D	0.605	neutral	None	None	None	None	N
E/V	0.4329	ambiguous	0.4529	ambiguous	0.086	Stabilizing	1.0	D	0.64	neutral	N	0.489217474	None	None	N
E/W	0.9563	likely_pathogenic	0.9605	pathogenic	-0.053	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/Y	0.8127	likely_pathogenic	0.8331	pathogenic	0.099	Stabilizing	1.0	D	0.643	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.