TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25085	75478;75479;75480	chr2:178570879;178570878;178570877	chr2:179435606;179435605;179435604
N2AB	23444	70555;70556;70557	chr2:178570879;178570878;178570877	chr2:179435606;179435605;179435604
N2A	22517	67774;67775;67776	chr2:178570879;178570878;178570877	chr2:179435606;179435605;179435604
N2B	16020	48283;48284;48285	chr2:178570879;178570878;178570877	chr2:179435606;179435605;179435604
Novex-1	16145	48658;48659;48660	chr2:178570879;178570878;178570877	chr2:179435606;179435605;179435604
Novex-2	16212	48859;48860;48861	chr2:178570879;178570878;178570877	chr2:179435606;179435605;179435604
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: Fn3-70
• Domain position: 80
• Structural Position: 112
• Q(SASA): 0.1356
• 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/Y	None	None	0.998	D	0.795	0.519	0.675916937895	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

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	0.9952	likely_pathogenic	0.9944	pathogenic	0.188	Stabilizing	0.938	D	0.707	prob.neutral	None	None	None	None	N
N/C	0.9627	likely_pathogenic	0.9583	pathogenic	-0.175	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
N/D	0.9596	likely_pathogenic	0.961	pathogenic	-2.263	Highly Destabilizing	0.958	D	0.611	neutral	D	0.540250178	None	None	N
N/E	0.9978	likely_pathogenic	0.9976	pathogenic	-2.15	Highly Destabilizing	0.968	D	0.688	prob.neutral	None	None	None	None	N
N/F	0.9989	likely_pathogenic	0.9988	pathogenic	-0.208	Destabilizing	0.995	D	0.798	deleterious	None	None	None	None	N
N/G	0.9852	likely_pathogenic	0.9817	pathogenic	-0.058	Destabilizing	0.968	D	0.581	neutral	None	None	None	None	N
N/H	0.9682	likely_pathogenic	0.9636	pathogenic	-0.089	Destabilizing	0.998	D	0.708	prob.delet.	D	0.542531584	None	None	N
N/I	0.9901	likely_pathogenic	0.9887	pathogenic	0.765	Stabilizing	0.988	D	0.803	deleterious	D	0.554394868	None	None	N
N/K	0.9977	likely_pathogenic	0.9973	pathogenic	0.255	Stabilizing	0.958	D	0.695	prob.neutral	D	0.552873931	None	None	N
N/L	0.9755	likely_pathogenic	0.9714	pathogenic	0.765	Stabilizing	0.982	D	0.773	deleterious	None	None	None	None	N
N/M	0.9854	likely_pathogenic	0.9844	pathogenic	0.969	Stabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
N/P	0.9974	likely_pathogenic	0.9967	pathogenic	0.601	Stabilizing	0.995	D	0.785	deleterious	None	None	None	None	N
N/Q	0.9977	likely_pathogenic	0.9973	pathogenic	-0.887	Destabilizing	0.995	D	0.756	deleterious	None	None	None	None	N
N/R	0.9974	likely_pathogenic	0.9968	pathogenic	0.337	Stabilizing	0.991	D	0.758	deleterious	None	None	None	None	N
N/S	0.788	likely_pathogenic	0.7657	pathogenic	-0.468	Destabilizing	0.919	D	0.587	neutral	N	0.514890994	None	None	N
N/T	0.881	likely_pathogenic	0.8731	pathogenic	-0.226	Destabilizing	0.067	N	0.358	neutral	N	0.519864517	None	None	N
N/V	0.9868	likely_pathogenic	0.9847	pathogenic	0.601	Stabilizing	0.982	D	0.785	deleterious	None	None	None	None	N
N/W	0.9996	likely_pathogenic	0.9996	pathogenic	-0.382	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
N/Y	0.9896	likely_pathogenic	0.9884	pathogenic	0.217	Stabilizing	0.998	D	0.795	deleterious	D	0.553887889	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.