TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24041	72346;72347;72348	chr2:178574011;178574010;178574009	chr2:179438738;179438737;179438736
N2AB	22400	67423;67424;67425	chr2:178574011;178574010;178574009	chr2:179438738;179438737;179438736
N2A	21473	64642;64643;64644	chr2:178574011;178574010;178574009	chr2:179438738;179438737;179438736
N2B	14976	45151;45152;45153	chr2:178574011;178574010;178574009	chr2:179438738;179438737;179438736
Novex-1	15101	45526;45527;45528	chr2:178574011;178574010;178574009	chr2:179438738;179438737;179438736
Novex-2	15168	45727;45728;45729	chr2:178574011;178574010;178574009	chr2:179438738;179438737;179438736
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-131
• Domain position: 13
• Structural Position: 16
• Q(SASA): 0.3936
• 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/S	rs1245486609	-1.74	0.497	N	0.52	0.451	0.803963018184	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/S	rs1245486609	-1.74	0.497	N	0.52	0.451	0.803963018184	gnomAD-4.0.0	1.59218E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43312E-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
L/A	0.3971	ambiguous	0.4177	ambiguous	-2.364	Highly Destabilizing	0.072	N	0.406	neutral	None	None	None	None	I
L/C	0.4419	ambiguous	0.4484	ambiguous	-1.665	Destabilizing	0.968	D	0.483	neutral	None	None	None	None	I
L/D	0.9287	likely_pathogenic	0.9403	pathogenic	-2.323	Highly Destabilizing	0.726	D	0.595	neutral	None	None	None	None	I
L/E	0.6595	likely_pathogenic	0.6909	pathogenic	-2.141	Highly Destabilizing	0.726	D	0.589	neutral	None	None	None	None	I
L/F	0.2336	likely_benign	0.2736	benign	-1.398	Destabilizing	0.497	N	0.467	neutral	N	0.496965458	None	None	I
L/G	0.7402	likely_pathogenic	0.7416	pathogenic	-2.865	Highly Destabilizing	0.726	D	0.596	neutral	None	None	None	None	I
L/H	0.4352	ambiguous	0.5014	ambiguous	-2.219	Highly Destabilizing	0.968	D	0.615	neutral	None	None	None	None	I
L/I	0.076	likely_benign	0.0814	benign	-0.945	Destabilizing	0.001	N	0.179	neutral	N	0.388872414	None	None	I
L/K	0.4726	ambiguous	0.4843	ambiguous	-1.837	Destabilizing	0.726	D	0.531	neutral	None	None	None	None	I
L/M	0.1578	likely_benign	0.1611	benign	-0.894	Destabilizing	0.567	D	0.499	neutral	None	None	None	None	I
L/N	0.7309	likely_pathogenic	0.7317	pathogenic	-2.041	Highly Destabilizing	0.89	D	0.605	neutral	None	None	None	None	I
L/P	0.8955	likely_pathogenic	0.918	pathogenic	-1.395	Destabilizing	0.89	D	0.595	neutral	None	None	None	None	I
L/Q	0.3128	likely_benign	0.3437	ambiguous	-1.968	Destabilizing	0.89	D	0.547	neutral	None	None	None	None	I
L/R	0.3243	likely_benign	0.3587	ambiguous	-1.464	Destabilizing	0.726	D	0.543	neutral	None	None	None	None	I
L/S	0.546	ambiguous	0.596	pathogenic	-2.757	Highly Destabilizing	0.497	N	0.52	neutral	N	0.506123659	None	None	I
L/T	0.3283	likely_benign	0.324	benign	-2.438	Highly Destabilizing	0.272	N	0.447	neutral	None	None	None	None	I
L/V	0.0684	likely_benign	0.0747	benign	-1.395	Destabilizing	None	N	0.169	neutral	N	0.326626302	None	None	I
L/W	0.4629	ambiguous	0.5737	pathogenic	-1.717	Destabilizing	0.968	D	0.601	neutral	None	None	None	None	I
L/Y	0.5511	ambiguous	0.6127	pathogenic	-1.433	Destabilizing	0.726	D	0.468	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.