TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15396	46411;46412;46413	chr2:178620335;178620334;178620333	chr2:179485062;179485061;179485060
N2AB	13755	41488;41489;41490	chr2:178620335;178620334;178620333	chr2:179485062;179485061;179485060
N2A	12828	38707;38708;38709	chr2:178620335;178620334;178620333	chr2:179485062;179485061;179485060
N2B	6331	19216;19217;19218	chr2:178620335;178620334;178620333	chr2:179485062;179485061;179485060
Novex-1	6456	19591;19592;19593	chr2:178620335;178620334;178620333	chr2:179485062;179485061;179485060
Novex-2	6523	19792;19793;19794	chr2:178620335;178620334;178620333	chr2:179485062;179485061;179485060
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-106
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.7007
• 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
H/P	None	None	0.004	N	0.371	0.256	0.267755039894	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

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
H/A	0.4133	ambiguous	0.5144	ambiguous	-0.25	Destabilizing	0.25	N	0.487	neutral	None	None	None	None	N
H/C	0.4354	ambiguous	0.5264	ambiguous	0.346	Stabilizing	0.992	D	0.498	neutral	None	None	None	None	N
H/D	0.3974	ambiguous	0.4482	ambiguous	0.097	Stabilizing	0.379	N	0.527	neutral	N	0.506002915	None	None	N
H/E	0.457	ambiguous	0.5558	ambiguous	0.157	Stabilizing	0.25	N	0.492	neutral	None	None	None	None	N
H/F	0.41	ambiguous	0.4934	ambiguous	0.684	Stabilizing	0.972	D	0.518	neutral	None	None	None	None	N
H/G	0.4969	ambiguous	0.5966	pathogenic	-0.573	Destabilizing	0.447	N	0.503	neutral	None	None	None	None	N
H/I	0.4992	ambiguous	0.616	pathogenic	0.604	Stabilizing	0.92	D	0.503	neutral	None	None	None	None	N
H/K	0.3327	likely_benign	0.4177	ambiguous	-0.082	Destabilizing	0.447	N	0.526	neutral	None	None	None	None	N
H/L	0.2024	likely_benign	0.2595	benign	0.604	Stabilizing	0.549	D	0.521	neutral	N	0.470419325	None	None	N
H/M	0.5251	ambiguous	0.6413	pathogenic	0.394	Stabilizing	0.972	D	0.479	neutral	None	None	None	None	N
H/N	0.155	likely_benign	0.1757	benign	-0.106	Destabilizing	0.004	N	0.175	neutral	N	0.494673186	None	None	N
H/P	0.179	likely_benign	0.1737	benign	0.344	Stabilizing	0.004	N	0.371	neutral	N	0.435998329	None	None	N
H/Q	0.2752	likely_benign	0.3608	ambiguous	0.041	Stabilizing	0.045	N	0.149	neutral	N	0.466143278	None	None	N
H/R	0.1982	likely_benign	0.259	benign	-0.546	Destabilizing	0.549	D	0.483	neutral	N	0.487232408	None	None	N
H/S	0.3531	ambiguous	0.4359	ambiguous	-0.187	Destabilizing	0.447	N	0.53	neutral	None	None	None	None	N
H/T	0.4065	ambiguous	0.552	ambiguous	-0.02	Destabilizing	0.617	D	0.493	neutral	None	None	None	None	N
H/V	0.4087	ambiguous	0.5324	ambiguous	0.344	Stabilizing	0.617	D	0.517	neutral	None	None	None	None	N
H/W	0.5809	likely_pathogenic	0.6513	pathogenic	0.886	Stabilizing	0.992	D	0.499	neutral	None	None	None	None	N
H/Y	0.1557	likely_benign	0.1819	benign	1.062	Stabilizing	0.963	D	0.492	neutral	N	0.508190801	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.