TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24089	72490;72491;72492	chr2:178573867;178573866;178573865	chr2:179438594;179438593;179438592
N2AB	22448	67567;67568;67569	chr2:178573867;178573866;178573865	chr2:179438594;179438593;179438592
N2A	21521	64786;64787;64788	chr2:178573867;178573866;178573865	chr2:179438594;179438593;179438592
N2B	15024	45295;45296;45297	chr2:178573867;178573866;178573865	chr2:179438594;179438593;179438592
Novex-1	15149	45670;45671;45672	chr2:178573867;178573866;178573865	chr2:179438594;179438593;179438592
Novex-2	15216	45871;45872;45873	chr2:178573867;178573866;178573865	chr2:179438594;179438593;179438592
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-131
• Domain position: 61
• Structural Position: 140
• Q(SASA): 0.1026
• 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
N/K	None	None	0.684	N	0.668	0.201	0.212008924253	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
N/Y	rs1709123437	None	0.979	N	0.85	0.367	0.546607571196	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/Y	rs1709123437	None	0.979	N	0.85	0.367	0.546607571196	gnomAD-4.0.0	2.57093E-06	None	None	None	None	N	None	3.38822E-05	0	None	0	0	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
N/A	0.3915	ambiguous	0.3642	ambiguous	-1.098	Destabilizing	0.373	N	0.74	deleterious	None	None	None	None	N
N/C	0.1706	likely_benign	0.1586	benign	-0.446	Destabilizing	0.02	N	0.693	prob.neutral	None	None	None	None	N
N/D	0.5465	ambiguous	0.5651	pathogenic	-1.733	Destabilizing	0.684	D	0.634	neutral	N	0.511297405	None	None	N
N/E	0.7995	likely_pathogenic	0.8097	pathogenic	-1.48	Destabilizing	0.742	D	0.667	neutral	None	None	None	None	N
N/F	0.6933	likely_pathogenic	0.7177	pathogenic	-0.554	Destabilizing	0.953	D	0.867	deleterious	None	None	None	None	N
N/G	0.6031	likely_pathogenic	0.5976	pathogenic	-1.533	Destabilizing	0.742	D	0.645	neutral	None	None	None	None	N
N/H	0.1623	likely_benign	0.1784	benign	-0.987	Destabilizing	0.979	D	0.683	prob.neutral	N	0.511124047	None	None	N
N/I	0.1498	likely_benign	0.1441	benign	0.073	Stabilizing	0.521	D	0.821	deleterious	N	0.279069137	None	None	N
N/K	0.6802	likely_pathogenic	0.7256	pathogenic	-0.245	Destabilizing	0.684	D	0.668	neutral	N	0.473683167	None	None	N
N/L	0.2718	likely_benign	0.2784	benign	0.073	Stabilizing	0.59	D	0.787	deleterious	None	None	None	None	N
N/M	0.3779	ambiguous	0.3863	ambiguous	0.336	Stabilizing	0.987	D	0.861	deleterious	None	None	None	None	N
N/P	0.9255	likely_pathogenic	0.927	pathogenic	-0.289	Destabilizing	0.953	D	0.85	deleterious	None	None	None	None	N
N/Q	0.5686	likely_pathogenic	0.5954	pathogenic	-0.956	Destabilizing	0.953	D	0.707	prob.neutral	None	None	None	None	N
N/R	0.6916	likely_pathogenic	0.7231	pathogenic	-0.468	Destabilizing	0.953	D	0.701	prob.neutral	None	None	None	None	N
N/S	0.111	likely_benign	0.1137	benign	-1.367	Destabilizing	0.078	N	0.383	neutral	N	0.481494573	None	None	N
N/T	0.2067	likely_benign	0.2153	benign	-0.905	Destabilizing	0.521	D	0.649	neutral	N	0.481147857	None	None	N
N/V	0.1557	likely_benign	0.1472	benign	-0.289	Destabilizing	0.02	N	0.629	neutral	None	None	None	None	N
N/W	0.8625	likely_pathogenic	0.8799	pathogenic	-0.414	Destabilizing	0.996	D	0.853	deleterious	None	None	None	None	N
N/Y	0.2429	likely_benign	0.2519	benign	-0.08	Destabilizing	0.979	D	0.85	deleterious	N	0.481494573	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.