TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5083	15472;15473;15474	chr2:178734577;178734576;178734575	chr2:179599304;179599303;179599302
N2AB	4766	14521;14522;14523	chr2:178734577;178734576;178734575	chr2:179599304;179599303;179599302
N2A	3839	11740;11741;11742	chr2:178734577;178734576;178734575	chr2:179599304;179599303;179599302
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-34
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5436
• 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
P/A	None	None	0.183	D	0.301	0.27	0.231231049324	gnomAD-4.0.0	9.80048E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.27838E-05	0	0
P/T	rs1465484453	None	0.003	N	0.107	0.225	0.332133492242	gnomAD-4.0.0	1.40007E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.82626E-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
P/A	0.0955	likely_benign	0.0735	benign	-0.425	Destabilizing	0.183	N	0.301	neutral	D	0.543364656	None	None	N
P/C	0.6754	likely_pathogenic	0.5432	ambiguous	-0.368	Destabilizing	0.983	D	0.369	neutral	None	None	None	None	N
P/D	0.5348	ambiguous	0.3749	ambiguous	-0.679	Destabilizing	0.418	N	0.403	neutral	None	None	None	None	N
P/E	0.3602	ambiguous	0.2501	benign	-0.819	Destabilizing	0.418	N	0.331	neutral	None	None	None	None	N
P/F	0.6927	likely_pathogenic	0.5295	ambiguous	-0.842	Destabilizing	0.002	N	0.223	neutral	None	None	None	None	N
P/G	0.4262	ambiguous	0.2888	benign	-0.529	Destabilizing	0.418	N	0.379	neutral	None	None	None	None	N
P/H	0.3172	likely_benign	0.2108	benign	-0.259	Destabilizing	0.794	D	0.361	neutral	D	0.656200999	None	None	N
P/I	0.4786	ambiguous	0.3534	ambiguous	-0.307	Destabilizing	0.264	N	0.375	neutral	None	None	None	None	N
P/K	0.3941	ambiguous	0.2774	benign	-0.433	Destabilizing	0.264	N	0.303	neutral	None	None	None	None	N
P/L	0.1851	likely_benign	0.1418	benign	-0.307	Destabilizing	0.001	N	0.16	neutral	N	0.520880958	None	None	N
P/M	0.4213	ambiguous	0.3089	benign	-0.259	Destabilizing	0.061	N	0.211	neutral	None	None	None	None	N
P/N	0.4387	ambiguous	0.2854	benign	-0.04	Destabilizing	0.418	N	0.462	neutral	None	None	None	None	N
P/Q	0.2377	likely_benign	0.1576	benign	-0.357	Destabilizing	0.716	D	0.43	neutral	None	None	None	None	N
P/R	0.2774	likely_benign	0.1912	benign	0.127	Stabilizing	0.002	N	0.211	neutral	D	0.598540719	None	None	N
P/S	0.1821	likely_benign	0.1179	benign	-0.273	Destabilizing	0.101	N	0.307	neutral	N	0.514246674	None	None	N
P/T	0.1494	likely_benign	0.1022	benign	-0.33	Destabilizing	0.003	N	0.107	neutral	N	0.515242999	None	None	N
P/V	0.3172	likely_benign	0.2329	benign	-0.313	Destabilizing	0.129	N	0.305	neutral	None	None	None	None	N
P/W	0.839	likely_pathogenic	0.719	pathogenic	-0.931	Destabilizing	0.983	D	0.373	neutral	None	None	None	None	N
P/Y	0.6323	likely_pathogenic	0.4764	ambiguous	-0.624	Destabilizing	0.557	D	0.475	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.