TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9942	30049;30050;30051	chr2:178704648;178704647;178704646	chr2:179569375;179569374;179569373
N2AB	9625	29098;29099;29100	chr2:178704648;178704647;178704646	chr2:179569375;179569374;179569373
N2A	8698	26317;26318;26319	chr2:178704648;178704647;178704646	chr2:179569375;179569374;179569373
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-84
• Domain position: 43
• Structural Position: 59
• Q(SASA): 0.2867
• 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/D	None	None	0.002	None	0.131	0.051	0.144782658237	gnomAD-4.0.0	1.59497E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4367E-05	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	0.149	likely_benign	0.1799	benign	-0.13	Destabilizing	0.016	N	0.124	neutral	None	None	None	None	N
E/C	0.875	likely_pathogenic	0.8952	pathogenic	-0.362	Destabilizing	0.992	D	0.401	neutral	None	None	None	None	N
E/D	0.1295	likely_benign	0.133	benign	-0.401	Destabilizing	0.002	N	0.131	neutral	None	None	None	None	N
E/F	0.6661	likely_pathogenic	0.7218	pathogenic	0.161	Stabilizing	0.85	D	0.419	neutral	None	None	None	None	N
E/G	0.2019	likely_benign	0.2614	benign	-0.324	Destabilizing	0.002	N	0.166	neutral	None	None	None	None	N
E/H	0.4659	ambiguous	0.5389	ambiguous	0.736	Stabilizing	0.972	D	0.385	neutral	None	None	None	None	N
E/I	0.2791	likely_benign	0.3405	ambiguous	0.348	Stabilizing	0.447	N	0.424	neutral	None	None	None	None	N
E/K	0.1728	likely_benign	0.2438	benign	0.363	Stabilizing	0.549	D	0.383	neutral	None	None	None	None	N
E/L	0.2857	likely_benign	0.3341	benign	0.348	Stabilizing	0.447	N	0.448	neutral	None	None	None	None	N
E/M	0.4002	ambiguous	0.46	ambiguous	0.076	Stabilizing	0.92	D	0.387	neutral	None	None	None	None	N
E/N	0.2123	likely_benign	0.2586	benign	-0.217	Destabilizing	0.447	N	0.383	neutral	None	None	None	None	N
E/P	0.5811	likely_pathogenic	0.6283	pathogenic	0.209	Stabilizing	0.92	D	0.429	neutral	None	None	None	None	N
E/Q	0.1398	likely_benign	0.1731	benign	-0.129	Destabilizing	0.712	D	0.399	neutral	None	None	None	None	N
E/R	0.31	likely_benign	0.3991	ambiguous	0.736	Stabilizing	0.92	D	0.393	neutral	None	None	None	None	N
E/S	0.1756	likely_benign	0.2182	benign	-0.32	Destabilizing	0.25	N	0.369	neutral	None	None	None	None	N
E/T	0.202	likely_benign	0.2507	benign	-0.14	Destabilizing	0.617	D	0.409	neutral	None	None	None	None	N
E/V	0.1848	likely_benign	0.2191	benign	0.209	Stabilizing	0.004	N	0.245	neutral	None	None	None	None	N
E/W	0.904	likely_pathogenic	0.9279	pathogenic	0.314	Stabilizing	0.992	D	0.462	neutral	None	None	None	None	N
E/Y	0.5864	likely_pathogenic	0.6485	pathogenic	0.41	Stabilizing	0.92	D	0.411	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.