TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25569	76930;76931;76932	chr2:178569427;178569426;178569425	chr2:179434154;179434153;179434152
N2AB	23928	72007;72008;72009	chr2:178569427;178569426;178569425	chr2:179434154;179434153;179434152
N2A	23001	69226;69227;69228	chr2:178569427;178569426;178569425	chr2:179434154;179434153;179434152
N2B	16504	49735;49736;49737	chr2:178569427;178569426;178569425	chr2:179434154;179434153;179434152
Novex-1	16629	50110;50111;50112	chr2:178569427;178569426;178569425	chr2:179434154;179434153;179434152
Novex-2	16696	50311;50312;50313	chr2:178569427;178569426;178569425	chr2:179434154;179434153;179434152
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-135
• Domain position: 56
• Structural Position: 141
• Q(SASA): 0.8046
• Predicted PPI site: I

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
D/E	rs1002726225	None	0.001	N	0.178	0.055	0.165133752707	gnomAD-4.0.0	2.73767E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59851E-06	0	0
D/H	None	None	0.879	N	0.479	0.442	0.336400405673	gnomAD-4.0.0	1.5924E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85984E-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
D/A	0.2877	likely_benign	0.2874	benign	-0.443	Destabilizing	0.338	N	0.507	neutral	N	0.49836818	None	None	I
D/C	0.7386	likely_pathogenic	0.7441	pathogenic	0.096	Stabilizing	0.991	D	0.615	neutral	None	None	None	None	I
D/E	0.1385	likely_benign	0.1337	benign	-0.379	Destabilizing	0.001	N	0.178	neutral	N	0.428084163	None	None	I
D/F	0.8037	likely_pathogenic	0.8108	pathogenic	-0.412	Destabilizing	0.967	D	0.56	neutral	None	None	None	None	I
D/G	0.2206	likely_benign	0.2201	benign	-0.675	Destabilizing	0.505	D	0.468	neutral	N	0.48988477	None	None	I
D/H	0.4407	ambiguous	0.4372	ambiguous	-0.54	Destabilizing	0.879	D	0.479	neutral	N	0.519340885	None	None	I
D/I	0.6116	likely_pathogenic	0.6121	pathogenic	0.131	Stabilizing	0.906	D	0.557	neutral	None	None	None	None	I
D/K	0.5431	ambiguous	0.534	ambiguous	0.298	Stabilizing	0.404	N	0.473	neutral	None	None	None	None	I
D/L	0.5558	ambiguous	0.5628	ambiguous	0.131	Stabilizing	0.826	D	0.493	neutral	None	None	None	None	I
D/M	0.7723	likely_pathogenic	0.7765	pathogenic	0.473	Stabilizing	0.991	D	0.563	neutral	None	None	None	None	I
D/N	0.1544	likely_benign	0.148	benign	-0.031	Destabilizing	0.505	D	0.455	neutral	N	0.501139127	None	None	I
D/P	0.6197	likely_pathogenic	0.607	pathogenic	-0.038	Destabilizing	0.004	N	0.264	neutral	None	None	None	None	I
D/Q	0.402	ambiguous	0.4073	ambiguous	-0.005	Destabilizing	0.404	N	0.402	neutral	None	None	None	None	I
D/R	0.5973	likely_pathogenic	0.5984	pathogenic	0.322	Stabilizing	0.826	D	0.501	neutral	None	None	None	None	I
D/S	0.1925	likely_benign	0.1925	benign	-0.175	Destabilizing	0.404	N	0.44	neutral	None	None	None	None	I
D/T	0.3739	ambiguous	0.3764	ambiguous	0.012	Stabilizing	0.575	D	0.465	neutral	None	None	None	None	I
D/V	0.3776	ambiguous	0.3808	ambiguous	-0.038	Destabilizing	0.782	D	0.469	neutral	N	0.511164119	None	None	I
D/W	0.9402	likely_pathogenic	0.9424	pathogenic	-0.259	Destabilizing	0.991	D	0.647	neutral	None	None	None	None	I
D/Y	0.4048	ambiguous	0.4096	ambiguous	-0.159	Destabilizing	0.957	D	0.565	neutral	N	0.512606914	None	None	I

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.