TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2636	8131;8132;8133	chr2:178771421;178771420;178771419	chr2:179636148;179636147;179636146
N2AB	2636	8131;8132;8133	chr2:178771421;178771420;178771419	chr2:179636148;179636147;179636146
N2A	2636	8131;8132;8133	chr2:178771421;178771420;178771419	chr2:179636148;179636147;179636146
N2B	2590	7993;7994;7995	chr2:178771421;178771420;178771419	chr2:179636148;179636147;179636146
Novex-1	2590	7993;7994;7995	chr2:178771421;178771420;178771419	chr2:179636148;179636147;179636146
Novex-2	2590	7993;7994;7995	chr2:178771421;178771420;178771419	chr2:179636148;179636147;179636146
Novex-3	2636	8131;8132;8133	chr2:178771421;178771420;178771419	chr2:179636148;179636147;179636146

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-16
• Domain position: 16
• Structural Position: 26
• Q(SASA): 0.5568
• 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
E/V	rs1207371966	0.189	0.01	N	0.228	0.335	0.417208245017	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.81E-06	0
E/V	rs1207371966	0.189	0.01	N	0.228	0.335	0.417208245017	gnomAD-4.0.0	3.18187E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.715E-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
E/A	0.1279	likely_benign	0.1362	benign	-0.847	Destabilizing	0.139	N	0.253	neutral	N	0.445197897	None	None	N
E/C	0.8483	likely_pathogenic	0.8542	pathogenic	-0.383	Destabilizing	0.995	D	0.322	neutral	None	None	None	None	N
E/D	0.1686	likely_benign	0.1736	benign	-0.762	Destabilizing	0.425	N	0.301	neutral	N	0.431115871	None	None	N
E/F	0.7265	likely_pathogenic	0.7319	pathogenic	-0.381	Destabilizing	0.944	D	0.378	neutral	None	None	None	None	N
E/G	0.1741	likely_benign	0.1738	benign	-1.145	Destabilizing	0.425	N	0.361	neutral	N	0.504062077	None	None	N
E/H	0.493	ambiguous	0.4927	ambiguous	-0.359	Destabilizing	0.944	D	0.369	neutral	None	None	None	None	N
E/I	0.2911	likely_benign	0.3047	benign	-0.053	Destabilizing	0.543	D	0.424	neutral	None	None	None	None	N
E/K	0.1208	likely_benign	0.1216	benign	-0.203	Destabilizing	0.27	N	0.296	neutral	N	0.43158041	None	None	N
E/L	0.3064	likely_benign	0.3172	benign	-0.053	Destabilizing	0.329	N	0.332	neutral	None	None	None	None	N
E/M	0.3595	ambiguous	0.3716	ambiguous	0.24	Stabilizing	0.944	D	0.339	neutral	None	None	None	None	N
E/N	0.2672	likely_benign	0.2809	benign	-0.716	Destabilizing	0.704	D	0.289	neutral	None	None	None	None	N
E/P	0.4379	ambiguous	0.4419	ambiguous	-0.297	Destabilizing	0.828	D	0.416	neutral	None	None	None	None	N
E/Q	0.1436	likely_benign	0.1452	benign	-0.637	Destabilizing	0.023	N	0.163	neutral	N	0.452411247	None	None	N
E/R	0.227	likely_benign	0.2198	benign	0.122	Stabilizing	0.007	N	0.17	neutral	None	None	None	None	N
E/S	0.2077	likely_benign	0.2237	benign	-0.948	Destabilizing	0.329	N	0.283	neutral	None	None	None	None	N
E/T	0.1565	likely_benign	0.1651	benign	-0.7	Destabilizing	0.004	N	0.183	neutral	None	None	None	None	N
E/V	0.1615	likely_benign	0.167	benign	-0.297	Destabilizing	0.01	N	0.228	neutral	N	0.479132707	None	None	N
E/W	0.8843	likely_pathogenic	0.878	pathogenic	-0.087	Destabilizing	0.995	D	0.335	neutral	None	None	None	None	N
E/Y	0.6035	likely_pathogenic	0.5969	pathogenic	-0.111	Destabilizing	0.981	D	0.407	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.