TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26234	78925;78926;78927	chr2:178567432;178567431;178567430	chr2:179432159;179432158;179432157
N2AB	24593	74002;74003;74004	chr2:178567432;178567431;178567430	chr2:179432159;179432158;179432157
N2A	23666	71221;71222;71223	chr2:178567432;178567431;178567430	chr2:179432159;179432158;179432157
N2B	17169	51730;51731;51732	chr2:178567432;178567431;178567430	chr2:179432159;179432158;179432157
Novex-1	17294	52105;52106;52107	chr2:178567432;178567431;178567430	chr2:179432159;179432158;179432157
Novex-2	17361	52306;52307;52308	chr2:178567432;178567431;178567430	chr2:179432159;179432158;179432157
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-137
• Domain position: 42
• Structural Position: 58
• Q(SASA): 0.2011
• 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
I/T	None	None	0.042	N	0.377	0.348	0.540107908424	gnomAD-4.0.0	1.6032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87305E-06	0	0
I/V	None	None	None	N	0.118	0.24	0.0806252709748	gnomAD-4.0.0	1.60302E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.42718E-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
I/A	0.4347	ambiguous	0.3296	benign	-2.28	Highly Destabilizing	None	N	0.193	neutral	None	None	None	None	N
I/C	0.8383	likely_pathogenic	0.7592	pathogenic	-1.461	Destabilizing	0.667	D	0.483	neutral	None	None	None	None	N
I/D	0.9563	likely_pathogenic	0.9263	pathogenic	-2.207	Highly Destabilizing	0.667	D	0.521	neutral	None	None	None	None	N
I/E	0.8894	likely_pathogenic	0.8398	pathogenic	-2.057	Highly Destabilizing	0.22	N	0.491	neutral	None	None	None	None	N
I/F	0.2633	likely_benign	0.1949	benign	-1.364	Destabilizing	0.096	N	0.411	neutral	N	0.51942103	None	None	N
I/G	0.858	likely_pathogenic	0.7859	pathogenic	-2.745	Highly Destabilizing	0.124	N	0.439	neutral	None	None	None	None	N
I/H	0.9041	likely_pathogenic	0.8327	pathogenic	-1.954	Destabilizing	0.958	D	0.499	neutral	None	None	None	None	N
I/K	0.8328	likely_pathogenic	0.7662	pathogenic	-1.83	Destabilizing	0.22	N	0.488	neutral	None	None	None	None	N
I/L	0.0961	likely_benign	0.0854	benign	-0.982	Destabilizing	None	N	0.093	neutral	N	0.412034488	None	None	N
I/M	0.1013	likely_benign	0.0872	benign	-0.817	Destabilizing	0.427	N	0.462	neutral	D	0.53379305	None	None	N
I/N	0.773	likely_pathogenic	0.692	pathogenic	-1.921	Destabilizing	0.602	D	0.501	neutral	N	0.507589835	None	None	N
I/P	0.8778	likely_pathogenic	0.8083	pathogenic	-1.391	Destabilizing	0.667	D	0.522	neutral	None	None	None	None	N
I/Q	0.8322	likely_pathogenic	0.7538	pathogenic	-1.914	Destabilizing	0.667	D	0.503	neutral	None	None	None	None	N
I/R	0.7634	likely_pathogenic	0.6749	pathogenic	-1.369	Destabilizing	0.667	D	0.517	neutral	None	None	None	None	N
I/S	0.6811	likely_pathogenic	0.5787	pathogenic	-2.582	Highly Destabilizing	0.096	N	0.404	neutral	D	0.527820458	None	None	N
I/T	0.3238	likely_benign	0.2442	benign	-2.295	Highly Destabilizing	0.042	N	0.377	neutral	N	0.518284123	None	None	N
I/V	0.0822	likely_benign	0.0717	benign	-1.391	Destabilizing	None	N	0.118	neutral	N	0.455406837	None	None	N
I/W	0.8678	likely_pathogenic	0.7649	pathogenic	-1.599	Destabilizing	0.958	D	0.529	neutral	None	None	None	None	N
I/Y	0.7536	likely_pathogenic	0.6453	pathogenic	-1.348	Destabilizing	0.667	D	0.503	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.