TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19651	59176;59177;59178	chr2:178593257;178593256;178593255	chr2:179457984;179457983;179457982
N2AB	18010	54253;54254;54255	chr2:178593257;178593256;178593255	chr2:179457984;179457983;179457982
N2A	17083	51472;51473;51474	chr2:178593257;178593256;178593255	chr2:179457984;179457983;179457982
N2B	10586	31981;31982;31983	chr2:178593257;178593256;178593255	chr2:179457984;179457983;179457982
Novex-1	10711	32356;32357;32358	chr2:178593257;178593256;178593255	chr2:179457984;179457983;179457982
Novex-2	10778	32557;32558;32559	chr2:178593257;178593256;178593255	chr2:179457984;179457983;179457982
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-30
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.1803
• 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	rs1442747427	None	0.999	N	0.608	0.423	0.432154444652	gnomAD-4.0.0	3.18392E-06	None	None	None	None	N	None	5.66059E-05	0	None	0	0	None	1.88239E-05	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	0.614	likely_pathogenic	0.5922	pathogenic	-2.118	Highly Destabilizing	0.999	D	0.658	neutral	N	0.499085053	None	None	N
E/C	0.9476	likely_pathogenic	0.9528	pathogenic	-1.124	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/D	0.7249	likely_pathogenic	0.7195	pathogenic	-1.7	Destabilizing	0.999	D	0.516	neutral	N	0.501162194	None	None	N
E/F	0.9633	likely_pathogenic	0.9641	pathogenic	-1.795	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/G	0.8583	likely_pathogenic	0.8441	pathogenic	-2.5	Highly Destabilizing	1.0	D	0.708	prob.delet.	N	0.518038682	None	None	N
E/H	0.9144	likely_pathogenic	0.9145	pathogenic	-1.599	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/I	0.6231	likely_pathogenic	0.6338	pathogenic	-1.004	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/K	0.7652	likely_pathogenic	0.7508	pathogenic	-1.888	Destabilizing	0.999	D	0.608	neutral	N	0.47214248	None	None	N
E/L	0.827	likely_pathogenic	0.8303	pathogenic	-1.004	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/M	0.7523	likely_pathogenic	0.7503	pathogenic	-0.175	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
E/N	0.8772	likely_pathogenic	0.875	pathogenic	-2.024	Highly Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
E/P	0.9984	likely_pathogenic	0.9986	pathogenic	-1.364	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/Q	0.325	likely_benign	0.325	benign	-1.737	Destabilizing	1.0	D	0.654	neutral	D	0.523503406	None	None	N
E/R	0.8391	likely_pathogenic	0.8394	pathogenic	-1.648	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/S	0.6662	likely_pathogenic	0.6535	pathogenic	-2.77	Highly Destabilizing	0.999	D	0.644	neutral	None	None	None	None	N
E/T	0.6789	likely_pathogenic	0.6784	pathogenic	-2.398	Highly Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/V	0.4843	ambiguous	0.482	ambiguous	-1.364	Destabilizing	1.0	D	0.703	prob.neutral	D	0.523772765	None	None	N
E/W	0.992	likely_pathogenic	0.9922	pathogenic	-1.807	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/Y	0.9489	likely_pathogenic	0.9487	pathogenic	-1.614	Destabilizing	1.0	D	0.743	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.