TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9169	27730;27731;27732	chr2:178712417;178712416;178712415	chr2:179577144;179577143;179577142
N2AB	8852	26779;26780;26781	chr2:178712417;178712416;178712415	chr2:179577144;179577143;179577142
N2A	7925	23998;23999;24000	chr2:178712417;178712416;178712415	chr2:179577144;179577143;179577142
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-77
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.068
• 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
L/M	None	None	1.0	D	0.809	0.622	0.822590732275	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
L/P	rs769078430	-1.835	1.0	D	0.901	0.854	0.92016668155	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
L/P	rs769078430	-1.835	1.0	D	0.901	0.854	0.92016668155	gnomAD-4.0.0	3.18227E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71595E-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
L/A	0.8996	likely_pathogenic	0.8695	pathogenic	-2.637	Highly Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
L/C	0.8796	likely_pathogenic	0.8629	pathogenic	-1.963	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9996	pathogenic	-3.592	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
L/E	0.9966	likely_pathogenic	0.9951	pathogenic	-3.276	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/F	0.3816	ambiguous	0.3362	benign	-1.676	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
L/G	0.9895	likely_pathogenic	0.9853	pathogenic	-3.22	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/H	0.9878	likely_pathogenic	0.9819	pathogenic	-2.989	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/I	0.1902	likely_benign	0.1724	benign	-0.878	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
L/K	0.994	likely_pathogenic	0.9915	pathogenic	-2.251	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/M	0.2206	likely_benign	0.2072	benign	-1.027	Destabilizing	1.0	D	0.809	deleterious	D	0.568453648	None	None	N
L/N	0.9979	likely_pathogenic	0.9969	pathogenic	-2.998	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/P	0.9987	likely_pathogenic	0.9976	pathogenic	-1.456	Destabilizing	1.0	D	0.901	deleterious	D	0.569974585	None	None	N
L/Q	0.9795	likely_pathogenic	0.9729	pathogenic	-2.646	Highly Destabilizing	1.0	D	0.9	deleterious	D	0.581330891	None	None	N
L/R	0.9842	likely_pathogenic	0.9778	pathogenic	-2.319	Highly Destabilizing	1.0	D	0.888	deleterious	D	0.581330891	None	None	N
L/S	0.9878	likely_pathogenic	0.9824	pathogenic	-3.491	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/T	0.9507	likely_pathogenic	0.9337	pathogenic	-3.012	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/V	0.225	likely_benign	0.2102	benign	-1.456	Destabilizing	0.999	D	0.7	prob.neutral	D	0.550095904	None	None	N
L/W	0.902	likely_pathogenic	0.8659	pathogenic	-2.104	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
L/Y	0.9426	likely_pathogenic	0.9255	pathogenic	-1.864	Destabilizing	1.0	D	0.859	deleterious	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.