TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9600	29023;29024;29025	chr2:178707769;178707768;178707767	chr2:179572496;179572495;179572494
N2AB	9283	28072;28073;28074	chr2:178707769;178707768;178707767	chr2:179572496;179572495;179572494
N2A	8356	25291;25292;25293	chr2:178707769;178707768;178707767	chr2:179572496;179572495;179572494
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-82
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.6112
• 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
T/I	None	None	0.901	None	0.499	0.338	0.527356302626	gnomAD-4.0.0	1.59213E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86041E-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
T/A	0.0949	likely_benign	0.0878	benign	-0.397	Destabilizing	0.008	N	0.144	neutral	None	None	None	None	N
T/C	0.5757	likely_pathogenic	0.5338	ambiguous	-0.371	Destabilizing	0.996	D	0.513	neutral	None	None	None	None	N
T/D	0.4144	ambiguous	0.3692	ambiguous	0.247	Stabilizing	0.923	D	0.454	neutral	None	None	None	None	N
T/E	0.3151	likely_benign	0.271	benign	0.203	Stabilizing	0.775	D	0.451	neutral	None	None	None	None	N
T/F	0.2713	likely_benign	0.2232	benign	-0.736	Destabilizing	0.961	D	0.594	neutral	None	None	None	None	N
T/G	0.3553	ambiguous	0.3133	benign	-0.576	Destabilizing	0.633	D	0.464	neutral	None	None	None	None	N
T/H	0.3182	likely_benign	0.2667	benign	-0.828	Destabilizing	0.989	D	0.573	neutral	None	None	None	None	N
T/I	0.1797	likely_benign	0.1556	benign	-0.04	Destabilizing	0.901	D	0.499	neutral	None	None	None	None	N
T/K	0.2669	likely_benign	0.2234	benign	-0.433	Destabilizing	0.565	D	0.456	neutral	None	None	None	None	N
T/L	0.123	likely_benign	0.1078	benign	-0.04	Destabilizing	0.775	D	0.473	neutral	None	None	None	None	N
T/M	0.0981	likely_benign	0.0848	benign	None	Stabilizing	0.996	D	0.499	neutral	None	None	None	None	N
T/N	0.1543	likely_benign	0.1384	benign	-0.314	Destabilizing	0.858	D	0.443	neutral	None	None	None	None	N
T/P	0.1946	likely_benign	0.1806	benign	-0.128	Destabilizing	0.949	D	0.498	neutral	None	None	None	None	N
T/Q	0.266	likely_benign	0.2289	benign	-0.471	Destabilizing	0.923	D	0.502	neutral	None	None	None	None	N
T/R	0.2019	likely_benign	0.1663	benign	-0.199	Destabilizing	0.901	D	0.497	neutral	None	None	None	None	N
T/S	0.1265	likely_benign	0.1163	benign	-0.546	Destabilizing	0.034	N	0.14	neutral	None	None	None	None	N
T/V	0.1461	likely_benign	0.132	benign	-0.128	Destabilizing	0.633	D	0.462	neutral	None	None	None	None	N
T/W	0.6311	likely_pathogenic	0.5532	ambiguous	-0.741	Destabilizing	0.996	D	0.668	neutral	None	None	None	None	N
T/Y	0.357	ambiguous	0.3151	benign	-0.46	Destabilizing	0.987	D	0.588	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.