TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6461	19606;19607;19608	chr2:178728545;178728544;178728543	chr2:179593272;179593271;179593270
N2AB	6144	18655;18656;18657	chr2:178728545;178728544;178728543	chr2:179593272;179593271;179593270
N2A	5217	15874;15875;15876	chr2:178728545;178728544;178728543	chr2:179593272;179593271;179593270
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-48
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1621
• 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	rs76771282	-0.197	1.0	D	0.755	0.527	0.289847578895	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
N/K	rs76771282	-0.197	1.0	D	0.755	0.527	0.289847578895	gnomAD-4.0.0	6.84733E-07	None	None	None	None	N	None	0	0	None	0	2.52704E-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
N/A	0.9982	likely_pathogenic	0.9983	pathogenic	-0.97	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
N/C	0.993	likely_pathogenic	0.9933	pathogenic	-0.494	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
N/D	0.9729	likely_pathogenic	0.9646	pathogenic	-1.71	Destabilizing	0.999	D	0.639	neutral	D	0.543371412	None	None	N
N/E	0.9984	likely_pathogenic	0.998	pathogenic	-1.553	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
N/F	0.9998	likely_pathogenic	0.9998	pathogenic	-0.758	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
N/G	0.9904	likely_pathogenic	0.9908	pathogenic	-1.311	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
N/H	0.9915	likely_pathogenic	0.9907	pathogenic	-0.947	Destabilizing	1.0	D	0.75	deleterious	D	0.556159749	None	None	N
N/I	0.9982	likely_pathogenic	0.9973	pathogenic	-0.089	Destabilizing	1.0	D	0.739	prob.delet.	D	0.556413239	None	None	N
N/K	0.9988	likely_pathogenic	0.9982	pathogenic	-0.253	Destabilizing	1.0	D	0.755	deleterious	D	0.55565277	None	None	N
N/L	0.9969	likely_pathogenic	0.9952	pathogenic	-0.089	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
N/M	0.9962	likely_pathogenic	0.9952	pathogenic	0.272	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
N/P	0.9996	likely_pathogenic	0.9994	pathogenic	-0.355	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
N/Q	0.9992	likely_pathogenic	0.999	pathogenic	-1.094	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
N/R	0.9987	likely_pathogenic	0.9982	pathogenic	-0.234	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
N/S	0.9301	likely_pathogenic	0.9407	pathogenic	-1.097	Destabilizing	0.999	D	0.6	neutral	N	0.507136449	None	None	N
N/T	0.9784	likely_pathogenic	0.9779	pathogenic	-0.762	Destabilizing	0.999	D	0.731	prob.delet.	N	0.509391401	None	None	N
N/V	0.9977	likely_pathogenic	0.9972	pathogenic	-0.355	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
N/W	0.9999	likely_pathogenic	0.9997	pathogenic	-0.579	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
N/Y	0.9962	likely_pathogenic	0.9938	pathogenic	-0.257	Destabilizing	1.0	D	0.762	deleterious	D	0.556159749	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.