TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29843	89752;89753;89754	chr2:178553373;178553372;178553371	chr2:179418100;179418099;179418098
N2AB	28202	84829;84830;84831	chr2:178553373;178553372;178553371	chr2:179418100;179418099;179418098
N2A	27275	82048;82049;82050	chr2:178553373;178553372;178553371	chr2:179418100;179418099;179418098
N2B	20778	62557;62558;62559	chr2:178553373;178553372;178553371	chr2:179418100;179418099;179418098
Novex-1	20903	62932;62933;62934	chr2:178553373;178553372;178553371	chr2:179418100;179418099;179418098
Novex-2	20970	63133;63134;63135	chr2:178553373;178553372;178553371	chr2:179418100;179418099;179418098
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-147
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.6229
• 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
V/A	None	None	0.37	N	0.289	0.182	0.397391247328	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/E	None	None	0.997	N	0.611	0.476	0.782665743468	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/M	rs376014865	None	0.997	N	0.501	0.207	None	gnomAD-4.0.0	1.38498E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.81122E-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
V/A	0.3143	likely_benign	0.2569	benign	-0.274	Destabilizing	0.37	N	0.289	neutral	N	0.413498713	None	None	N
V/C	0.9071	likely_pathogenic	0.8867	pathogenic	-0.621	Destabilizing	1.0	D	0.554	neutral	None	None	None	None	N
V/D	0.6921	likely_pathogenic	0.6121	pathogenic	-0.215	Destabilizing	0.998	D	0.644	neutral	None	None	None	None	N
V/E	0.6394	likely_pathogenic	0.5604	ambiguous	-0.338	Destabilizing	0.997	D	0.611	neutral	N	0.498501466	None	None	N
V/F	0.35	ambiguous	0.288	benign	-0.623	Destabilizing	0.998	D	0.535	neutral	None	None	None	None	N
V/G	0.472	ambiguous	0.398	ambiguous	-0.365	Destabilizing	0.994	D	0.564	neutral	N	0.499272258	None	None	N
V/H	0.8663	likely_pathogenic	0.8177	pathogenic	0.002	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
V/I	0.0963	likely_benign	0.0905	benign	-0.19	Destabilizing	0.437	N	0.286	neutral	None	None	None	None	N
V/K	0.7079	likely_pathogenic	0.6587	pathogenic	-0.308	Destabilizing	0.998	D	0.609	neutral	None	None	None	None	N
V/L	0.3973	ambiguous	0.3599	ambiguous	-0.19	Destabilizing	0.9	D	0.425	neutral	N	0.498848183	None	None	N
V/M	0.2744	likely_benign	0.2294	benign	-0.331	Destabilizing	0.997	D	0.501	neutral	N	0.499272258	None	None	N
V/N	0.5979	likely_pathogenic	0.5248	ambiguous	-0.07	Destabilizing	0.999	D	0.65	neutral	None	None	None	None	N
V/P	0.6914	likely_pathogenic	0.6434	pathogenic	-0.186	Destabilizing	0.998	D	0.587	neutral	None	None	None	None	N
V/Q	0.6972	likely_pathogenic	0.6241	pathogenic	-0.302	Destabilizing	0.999	D	0.598	neutral	None	None	None	None	N
V/R	0.6804	likely_pathogenic	0.6175	pathogenic	0.165	Stabilizing	0.998	D	0.649	neutral	None	None	None	None	N
V/S	0.4581	ambiguous	0.39	ambiguous	-0.396	Destabilizing	0.99	D	0.508	neutral	None	None	None	None	N
V/T	0.349	ambiguous	0.2978	benign	-0.422	Destabilizing	0.983	D	0.46	neutral	None	None	None	None	N
V/W	0.9384	likely_pathogenic	0.9064	pathogenic	-0.709	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
V/Y	0.786	likely_pathogenic	0.7235	pathogenic	-0.4	Destabilizing	0.999	D	0.533	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.