TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13837	41734;41735;41736	chr2:178636062;178636061;178636060	chr2:179500789;179500788;179500787
N2AB	12196	36811;36812;36813	chr2:178636062;178636061;178636060	chr2:179500789;179500788;179500787
N2A	11269	34030;34031;34032	chr2:178636062;178636061;178636060	chr2:179500789;179500788;179500787
N2B	4772	14539;14540;14541	chr2:178636062;178636061;178636060	chr2:179500789;179500788;179500787
Novex-1	4897	14914;14915;14916	chr2:178636062;178636061;178636060	chr2:179500789;179500788;179500787
Novex-2	4964	15115;15116;15117	chr2:178636062;178636061;178636060	chr2:179500789;179500788;179500787
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-88
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0615
• 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/V	None	None	0.022	N	0.284	0.115	0.276482976112	gnomAD-4.0.0	6.84402E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65695E-05

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	0.9703	likely_pathogenic	0.976	pathogenic	-2.261	Highly Destabilizing	0.067	N	0.581	neutral	None	None	None	None	N
L/C	0.9662	likely_pathogenic	0.9718	pathogenic	-1.616	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9997	pathogenic	-2.977	Highly Destabilizing	0.974	D	0.889	deleterious	None	None	None	None	N
L/E	0.9976	likely_pathogenic	0.9977	pathogenic	-2.676	Highly Destabilizing	0.974	D	0.87	deleterious	None	None	None	None	N
L/F	0.7185	likely_pathogenic	0.8017	pathogenic	-1.376	Destabilizing	0.949	D	0.749	deleterious	None	None	None	None	N
L/G	0.997	likely_pathogenic	0.997	pathogenic	-2.85	Highly Destabilizing	0.904	D	0.829	deleterious	None	None	None	None	N
L/H	0.9954	likely_pathogenic	0.9959	pathogenic	-2.553	Highly Destabilizing	0.998	D	0.86	deleterious	None	None	None	None	N
L/I	0.2943	likely_benign	0.3546	ambiguous	-0.522	Destabilizing	0.007	N	0.276	neutral	None	None	None	None	N
L/K	0.9954	likely_pathogenic	0.9954	pathogenic	-1.832	Destabilizing	0.949	D	0.838	deleterious	None	None	None	None	N
L/M	0.3892	ambiguous	0.4387	ambiguous	-0.611	Destabilizing	0.934	D	0.669	prob.neutral	N	0.492442361	None	None	N
L/N	0.9981	likely_pathogenic	0.9979	pathogenic	-2.458	Highly Destabilizing	0.991	D	0.887	deleterious	None	None	None	None	N
L/P	0.9988	likely_pathogenic	0.9986	pathogenic	-1.088	Destabilizing	0.966	D	0.891	deleterious	D	0.556985657	None	None	N
L/Q	0.9911	likely_pathogenic	0.9914	pathogenic	-2.148	Highly Destabilizing	0.989	D	0.86	deleterious	D	0.556985657	None	None	N
L/R	0.9918	likely_pathogenic	0.9921	pathogenic	-1.881	Destabilizing	0.966	D	0.883	deleterious	D	0.556985657	None	None	N
L/S	0.9966	likely_pathogenic	0.9972	pathogenic	-3.054	Highly Destabilizing	0.728	D	0.815	deleterious	None	None	None	None	N
L/T	0.9869	likely_pathogenic	0.9887	pathogenic	-2.583	Highly Destabilizing	0.842	D	0.831	deleterious	None	None	None	None	N
L/V	0.3499	ambiguous	0.4333	ambiguous	-1.088	Destabilizing	0.022	N	0.284	neutral	N	0.388709253	None	None	N
L/W	0.9773	likely_pathogenic	0.985	pathogenic	-1.812	Destabilizing	0.998	D	0.83	deleterious	None	None	None	None	N
L/Y	0.9823	likely_pathogenic	0.9868	pathogenic	-1.47	Destabilizing	0.991	D	0.851	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.