TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23147	69664;69665;69666	chr2:178576805;178576804;178576803	chr2:179441532;179441531;179441530
N2AB	21506	64741;64742;64743	chr2:178576805;178576804;178576803	chr2:179441532;179441531;179441530
N2A	20579	61960;61961;61962	chr2:178576805;178576804;178576803	chr2:179441532;179441531;179441530
N2B	14082	42469;42470;42471	chr2:178576805;178576804;178576803	chr2:179441532;179441531;179441530
Novex-1	14207	42844;42845;42846	chr2:178576805;178576804;178576803	chr2:179441532;179441531;179441530
Novex-2	14274	43045;43046;43047	chr2:178576805;178576804;178576803	chr2:179441532;179441531;179441530
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: Fn3-56
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5145
• 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	rs1173953424	-0.57	0.003	N	0.153	0.113	0.198526703765	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
E/D	rs1173953424	-0.57	0.003	N	0.153	0.113	0.198526703765	gnomAD-4.0.0	1.59336E-06	None	None	None	None	N	None	0	2.29221E-05	None	0	0	None	0	0	0	0	0
E/G	rs1396597790	-1.026	0.722	N	0.657	0.302	0.424073947737	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
E/G	rs1396597790	-1.026	0.722	N	0.657	0.302	0.424073947737	gnomAD-4.0.0	1.59349E-06	None	None	None	None	N	None	0	2.29305E-05	None	0	0	None	0	0	0	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	0.125	likely_benign	0.1258	benign	-0.54	Destabilizing	0.565	D	0.602	neutral	D	0.523097975	None	None	N
E/C	0.6734	likely_pathogenic	0.6778	pathogenic	-0.13	Destabilizing	0.996	D	0.803	deleterious	None	None	None	None	N
E/D	0.1554	likely_benign	0.1421	benign	-0.531	Destabilizing	0.003	N	0.153	neutral	N	0.472356289	None	None	N
E/F	0.6003	likely_pathogenic	0.5656	pathogenic	-0.34	Destabilizing	0.923	D	0.787	deleterious	None	None	None	None	N
E/G	0.2202	likely_benign	0.2184	benign	-0.765	Destabilizing	0.722	D	0.657	neutral	N	0.481750812	None	None	N
E/H	0.3167	likely_benign	0.3098	benign	-0.222	Destabilizing	0.996	D	0.569	neutral	None	None	None	None	N
E/I	0.1691	likely_benign	0.1599	benign	0.032	Stabilizing	0.858	D	0.716	prob.delet.	None	None	None	None	N
E/K	0.1165	likely_benign	0.1149	benign	0.194	Stabilizing	0.722	D	0.533	neutral	N	0.459699857	None	None	N
E/L	0.2392	likely_benign	0.2334	benign	0.032	Stabilizing	0.633	D	0.673	neutral	None	None	None	None	N
E/M	0.2794	likely_benign	0.27	benign	0.19	Stabilizing	0.989	D	0.765	deleterious	None	None	None	None	N
E/N	0.2333	likely_benign	0.2171	benign	-0.201	Destabilizing	0.858	D	0.545	neutral	None	None	None	None	N
E/P	0.9255	likely_pathogenic	0.917	pathogenic	-0.138	Destabilizing	0.961	D	0.723	prob.delet.	None	None	None	None	N
E/Q	0.103	likely_benign	0.1068	benign	-0.157	Destabilizing	0.949	D	0.55	neutral	N	0.45777706	None	None	N
E/R	0.1842	likely_benign	0.1826	benign	0.399	Stabilizing	0.961	D	0.577	neutral	None	None	None	None	N
E/S	0.1681	likely_benign	0.1631	benign	-0.355	Destabilizing	0.775	D	0.521	neutral	None	None	None	None	N
E/T	0.1417	likely_benign	0.1363	benign	-0.168	Destabilizing	0.775	D	0.645	neutral	None	None	None	None	N
E/V	0.1001	likely_benign	0.0981	benign	-0.138	Destabilizing	0.018	N	0.377	neutral	N	0.491140272	None	None	N
E/W	0.8221	likely_pathogenic	0.806	pathogenic	-0.143	Destabilizing	0.996	D	0.76	deleterious	None	None	None	None	N
E/Y	0.5126	ambiguous	0.4802	ambiguous	-0.086	Destabilizing	0.961	D	0.785	deleterious	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.