TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5961	18106;18107;18108	chr2:178730652;178730651;178730650	chr2:179595379;179595378;179595377
N2AB	5644	17155;17156;17157	chr2:178730652;178730651;178730650	chr2:179595379;179595378;179595377
N2A	4717	14374;14375;14376	chr2:178730652;178730651;178730650	chr2:179595379;179595378;179595377
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-43
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.4498
• 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/T	rs2080285790	None	0.103	N	0.212	0.089	0.203808441222	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.78469E-04
A/T	rs2080285790	None	0.103	N	0.212	0.089	0.203808441222	gnomAD-4.0.0	6.57428E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	4.78469E-04
A/V	rs909915866	None	0.896	N	0.369	0.235	0.374434639691	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	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
A/C	0.5903	likely_pathogenic	0.5717	pathogenic	-0.784	Destabilizing	0.999	D	0.43	neutral	None	None	None	None	N
A/D	0.2779	likely_benign	0.2748	benign	0.229	Stabilizing	0.059	N	0.261	neutral	N	0.474107241	None	None	N
A/E	0.2588	likely_benign	0.2749	benign	0.137	Stabilizing	0.851	D	0.409	neutral	None	None	None	None	N
A/F	0.3639	ambiguous	0.3762	ambiguous	-0.582	Destabilizing	0.996	D	0.55	neutral	None	None	None	None	N
A/G	0.1408	likely_benign	0.1371	benign	-0.358	Destabilizing	0.896	D	0.347	neutral	N	0.491327565	None	None	N
A/H	0.456	ambiguous	0.455	ambiguous	-0.267	Destabilizing	0.999	D	0.546	neutral	None	None	None	None	N
A/I	0.2615	likely_benign	0.277	benign	-0.117	Destabilizing	0.976	D	0.451	neutral	None	None	None	None	N
A/K	0.4382	ambiguous	0.4586	ambiguous	-0.446	Destabilizing	0.919	D	0.415	neutral	None	None	None	None	N
A/L	0.1798	likely_benign	0.1866	benign	-0.117	Destabilizing	0.919	D	0.413	neutral	None	None	None	None	N
A/M	0.2643	likely_benign	0.2785	benign	-0.43	Destabilizing	0.999	D	0.49	neutral	None	None	None	None	N
A/N	0.2387	likely_benign	0.238	benign	-0.269	Destabilizing	0.976	D	0.477	neutral	None	None	None	None	N
A/P	0.1022	likely_benign	0.0955	benign	-0.124	Destabilizing	0.059	N	0.21	neutral	N	0.436415645	None	None	N
A/Q	0.3333	likely_benign	0.3436	ambiguous	-0.379	Destabilizing	0.988	D	0.461	neutral	None	None	None	None	N
A/R	0.405	ambiguous	0.4211	ambiguous	-0.178	Destabilizing	0.988	D	0.454	neutral	None	None	None	None	N
A/S	0.0899	likely_benign	0.0884	benign	-0.607	Destabilizing	0.251	N	0.213	neutral	N	0.393411442	None	None	N
A/T	0.0899	likely_benign	0.093	benign	-0.587	Destabilizing	0.103	N	0.212	neutral	N	0.440456027	None	None	N
A/V	0.1373	likely_benign	0.1447	benign	-0.124	Destabilizing	0.896	D	0.369	neutral	N	0.498696254	None	None	N
A/W	0.7534	likely_pathogenic	0.7654	pathogenic	-0.776	Destabilizing	0.999	D	0.634	neutral	None	None	None	None	N
A/Y	0.4691	ambiguous	0.4875	ambiguous	-0.401	Destabilizing	0.996	D	0.546	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.