TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4952	15079;15080;15081	chr2:178735592;178735591;178735590	chr2:179600319;179600318;179600317
N2AB	4635	14128;14129;14130	chr2:178735592;178735591;178735590	chr2:179600319;179600318;179600317
N2A	3708	11347;11348;11349	chr2:178735592;178735591;178735590	chr2:179600319;179600318;179600317
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-32
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.758
• 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
L/M	rs781546825	-0.259	0.864	N	0.555	0.144	0.322230723748	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	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
L/A	0.1719	likely_benign	0.1847	benign	-0.946	Destabilizing	0.547	D	0.46	neutral	None	None	None	None	I
L/C	0.5079	ambiguous	0.4921	ambiguous	-0.794	Destabilizing	0.985	D	0.548	neutral	None	None	None	None	I
L/D	0.5472	ambiguous	0.5899	pathogenic	-0.262	Destabilizing	0.945	D	0.62	neutral	None	None	None	None	I
L/E	0.2612	likely_benign	0.2821	benign	-0.317	Destabilizing	0.945	D	0.613	neutral	None	None	None	None	I
L/F	0.132	likely_benign	0.1385	benign	-0.726	Destabilizing	0.894	D	0.531	neutral	None	None	None	None	I
L/G	0.3159	likely_benign	0.339	benign	-1.17	Destabilizing	0.945	D	0.611	neutral	None	None	None	None	I
L/H	0.2057	likely_benign	0.2223	benign	-0.321	Destabilizing	0.995	D	0.627	neutral	None	None	None	None	I
L/I	0.0697	likely_benign	0.07	benign	-0.455	Destabilizing	0.007	N	0.296	neutral	None	None	None	None	I
L/K	0.2064	likely_benign	0.2175	benign	-0.596	Destabilizing	0.945	D	0.552	neutral	None	None	None	None	I
L/M	0.0884	likely_benign	0.0948	benign	-0.496	Destabilizing	0.864	D	0.555	neutral	N	0.45477368	None	None	I
L/N	0.2626	likely_benign	0.289	benign	-0.425	Destabilizing	0.981	D	0.622	neutral	None	None	None	None	I
L/P	0.1256	likely_benign	0.1294	benign	-0.585	Destabilizing	0.975	D	0.621	neutral	N	0.424754471	None	None	I
L/Q	0.1108	likely_benign	0.1193	benign	-0.613	Destabilizing	0.975	D	0.566	neutral	N	0.424969322	None	None	I
L/R	0.1762	likely_benign	0.1752	benign	-0.015	Destabilizing	0.928	D	0.569	neutral	N	0.349772382	None	None	I
L/S	0.2064	likely_benign	0.2255	benign	-0.967	Destabilizing	0.894	D	0.553	neutral	None	None	None	None	I
L/T	0.1621	likely_benign	0.1747	benign	-0.904	Destabilizing	0.894	D	0.465	neutral	None	None	None	None	I
L/V	0.0731	likely_benign	0.0711	benign	-0.585	Destabilizing	0.006	N	0.247	neutral	N	0.45119108	None	None	I
L/W	0.2056	likely_benign	0.2072	benign	-0.733	Destabilizing	0.995	D	0.631	neutral	None	None	None	None	I
L/Y	0.2739	likely_benign	0.2918	benign	-0.508	Destabilizing	0.945	D	0.548	neutral	None	None	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.