TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28191	84796;84797;84798	chr2:178561561;178561560;178561559	chr2:179426288;179426287;179426286
N2AB	26550	79873;79874;79875	chr2:178561561;178561560;178561559	chr2:179426288;179426287;179426286
N2A	25623	77092;77093;77094	chr2:178561561;178561560;178561559	chr2:179426288;179426287;179426286
N2B	19126	57601;57602;57603	chr2:178561561;178561560;178561559	chr2:179426288;179426287;179426286
Novex-1	19251	57976;57977;57978	chr2:178561561;178561560;178561559	chr2:179426288;179426287;179426286
Novex-2	19318	58177;58178;58179	chr2:178561561;178561560;178561559	chr2:179426288;179426287;179426286
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-93
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.1251
• 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/P	None	None	0.999	N	0.895	0.65	0.853648971886	gnomAD-4.0.0	1.59245E-06	None	None	None	None	N	None	0	0	None	0	2.78056E-05	None	0	0	0	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	0.9006	likely_pathogenic	0.8972	pathogenic	-3.349	Highly Destabilizing	0.983	D	0.687	prob.neutral	None	None	None	None	N
L/C	0.8842	likely_pathogenic	0.8877	pathogenic	-2.487	Highly Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9997	pathogenic	-4.038	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
L/E	0.9963	likely_pathogenic	0.9963	pathogenic	-3.735	Highly Destabilizing	0.999	D	0.886	deleterious	None	None	None	None	N
L/F	0.8012	likely_pathogenic	0.8065	pathogenic	-2.11	Highly Destabilizing	0.997	D	0.67	neutral	N	0.517864552	None	None	N
L/G	0.9918	likely_pathogenic	0.9917	pathogenic	-3.898	Highly Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
L/H	0.9928	likely_pathogenic	0.9935	pathogenic	-3.402	Highly Destabilizing	1.0	D	0.868	deleterious	N	0.518118041	None	None	N
L/I	0.1131	likely_benign	0.1046	benign	-1.664	Destabilizing	0.37	N	0.293	neutral	N	0.423064266	None	None	N
L/K	0.9937	likely_pathogenic	0.9941	pathogenic	-2.886	Highly Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
L/M	0.3005	likely_benign	0.3018	benign	-1.761	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
L/N	0.9974	likely_pathogenic	0.9973	pathogenic	-3.609	Highly Destabilizing	0.999	D	0.897	deleterious	None	None	None	None	N
L/P	0.9963	likely_pathogenic	0.9962	pathogenic	-2.223	Highly Destabilizing	0.999	D	0.895	deleterious	N	0.518118041	None	None	N
L/Q	0.9852	likely_pathogenic	0.986	pathogenic	-3.295	Highly Destabilizing	0.999	D	0.889	deleterious	None	None	None	None	N
L/R	0.9872	likely_pathogenic	0.9875	pathogenic	-2.723	Highly Destabilizing	0.999	D	0.882	deleterious	N	0.518118041	None	None	N
L/S	0.9903	likely_pathogenic	0.9907	pathogenic	-4.088	Highly Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
L/T	0.9146	likely_pathogenic	0.9124	pathogenic	-3.643	Highly Destabilizing	0.998	D	0.752	deleterious	None	None	None	None	N
L/V	0.1101	likely_benign	0.1029	benign	-2.223	Highly Destabilizing	0.9	D	0.469	neutral	N	0.406262443	None	None	N
L/W	0.9837	likely_pathogenic	0.9852	pathogenic	-2.445	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/Y	0.9863	likely_pathogenic	0.9869	pathogenic	-2.377	Highly Destabilizing	0.999	D	0.779	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.