TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28565	85918;85919;85920	chr2:178560439;178560438;178560437	chr2:179425166;179425165;179425164
N2AB	26924	80995;80996;80997	chr2:178560439;178560438;178560437	chr2:179425166;179425165;179425164
N2A	25997	78214;78215;78216	chr2:178560439;178560438;178560437	chr2:179425166;179425165;179425164
N2B	19500	58723;58724;58725	chr2:178560439;178560438;178560437	chr2:179425166;179425165;179425164
Novex-1	19625	59098;59099;59100	chr2:178560439;178560438;178560437	chr2:179425166;179425165;179425164
Novex-2	19692	59299;59300;59301	chr2:178560439;178560438;178560437	chr2:179425166;179425165;179425164
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: Fn3-96
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.7459
• 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/Q	rs1703203626	None	0.117	N	0.451	0.14	0.128392430309	gnomAD-4.0.0	1.59174E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41196E-04	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	0.1763	likely_benign	0.18	benign	-0.633	Destabilizing	0.062	N	0.435	neutral	N	0.468418128	None	None	N
E/C	0.7808	likely_pathogenic	0.7772	pathogenic	-0.002	Destabilizing	0.935	D	0.585	neutral	None	None	None	None	N
E/D	0.0656	likely_benign	0.055	benign	-0.565	Destabilizing	None	N	0.109	neutral	N	0.3178251	None	None	N
E/F	0.6744	likely_pathogenic	0.6835	pathogenic	-0.589	Destabilizing	0.791	D	0.463	neutral	None	None	None	None	N
E/G	0.1499	likely_benign	0.1613	benign	-0.865	Destabilizing	0.062	N	0.45	neutral	N	0.418509382	None	None	N
E/H	0.4659	ambiguous	0.5089	ambiguous	-0.691	Destabilizing	0.555	D	0.375	neutral	None	None	None	None	N
E/I	0.4445	ambiguous	0.4299	ambiguous	-0.042	Destabilizing	0.555	D	0.462	neutral	None	None	None	None	N
E/K	0.3041	likely_benign	0.3811	ambiguous	0.137	Stabilizing	None	N	0.255	neutral	N	0.443655756	None	None	N
E/L	0.4311	ambiguous	0.4378	ambiguous	-0.042	Destabilizing	0.38	N	0.429	neutral	None	None	None	None	N
E/M	0.51	ambiguous	0.5171	ambiguous	0.332	Stabilizing	0.935	D	0.423	neutral	None	None	None	None	N
E/N	0.1594	likely_benign	0.1476	benign	-0.155	Destabilizing	0.001	N	0.255	neutral	None	None	None	None	N
E/P	0.8526	likely_pathogenic	0.8621	pathogenic	-0.218	Destabilizing	0.555	D	0.434	neutral	None	None	None	None	N
E/Q	0.2052	likely_benign	0.2405	benign	-0.135	Destabilizing	0.117	N	0.451	neutral	N	0.443367755	None	None	N
E/R	0.4172	ambiguous	0.5104	ambiguous	0.215	Stabilizing	0.235	N	0.377	neutral	None	None	None	None	N
E/S	0.1703	likely_benign	0.1637	benign	-0.353	Destabilizing	0.081	N	0.415	neutral	None	None	None	None	N
E/T	0.1921	likely_benign	0.1899	benign	-0.163	Destabilizing	0.149	N	0.426	neutral	None	None	None	None	N
E/V	0.2672	likely_benign	0.2695	benign	-0.218	Destabilizing	0.317	N	0.411	neutral	N	0.503608137	None	None	N
E/W	0.8724	likely_pathogenic	0.8931	pathogenic	-0.43	Destabilizing	0.935	D	0.617	neutral	None	None	None	None	N
E/Y	0.4926	ambiguous	0.4975	ambiguous	-0.341	Destabilizing	0.791	D	0.442	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.