TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19689	59290;59291;59292	chr2:178593054;178593053;178593052	chr2:179457781;179457780;179457779
N2AB	18048	54367;54368;54369	chr2:178593054;178593053;178593052	chr2:179457781;179457780;179457779
N2A	17121	51586;51587;51588	chr2:178593054;178593053;178593052	chr2:179457781;179457780;179457779
N2B	10624	32095;32096;32097	chr2:178593054;178593053;178593052	chr2:179457781;179457780;179457779
Novex-1	10749	32470;32471;32472	chr2:178593054;178593053;178593052	chr2:179457781;179457780;179457779
Novex-2	10816	32671;32672;32673	chr2:178593054;178593053;178593052	chr2:179457781;179457780;179457779
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-31
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.4177
• 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
A/V	None	None	0.767	N	0.249	0.254	0.316494231283	gnomAD-4.0.0	1.59227E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85972E-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
A/C	0.56	ambiguous	0.5671	pathogenic	-0.91	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
A/D	0.9134	likely_pathogenic	0.8391	pathogenic	-0.957	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
A/E	0.8461	likely_pathogenic	0.745	pathogenic	-0.963	Destabilizing	1.0	D	0.811	deleterious	N	0.48912478	None	None	N
A/F	0.7156	likely_pathogenic	0.6216	pathogenic	-0.844	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
A/G	0.3513	ambiguous	0.3022	benign	-1.089	Destabilizing	0.999	D	0.643	neutral	N	0.476589933	None	None	N
A/H	0.906	likely_pathogenic	0.8693	pathogenic	-1.156	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
A/I	0.2973	likely_benign	0.2235	benign	-0.197	Destabilizing	0.994	D	0.691	prob.neutral	None	None	None	None	N
A/K	0.9146	likely_pathogenic	0.8546	pathogenic	-1.154	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
A/L	0.4494	ambiguous	0.3647	ambiguous	-0.197	Destabilizing	0.994	D	0.603	neutral	None	None	None	None	N
A/M	0.487	ambiguous	0.3889	ambiguous	-0.287	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
A/N	0.7881	likely_pathogenic	0.6891	pathogenic	-0.934	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
A/P	0.3008	likely_benign	0.259	benign	-0.359	Destabilizing	1.0	D	0.833	deleterious	N	0.520351245	None	None	N
A/Q	0.8542	likely_pathogenic	0.7939	pathogenic	-1.028	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
A/R	0.8843	likely_pathogenic	0.8229	pathogenic	-0.843	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
A/S	0.2426	likely_benign	0.208	benign	-1.311	Destabilizing	0.998	D	0.634	neutral	N	0.47157673	None	None	N
A/T	0.2251	likely_benign	0.1591	benign	-1.203	Destabilizing	0.996	D	0.658	neutral	N	0.479401089	None	None	N
A/V	0.1413	likely_benign	0.1032	benign	-0.359	Destabilizing	0.767	D	0.249	neutral	N	0.390013272	None	None	N
A/W	0.9496	likely_pathogenic	0.9267	pathogenic	-1.196	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
A/Y	0.8153	likely_pathogenic	0.7623	pathogenic	-0.767	Destabilizing	1.0	D	0.857	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.