TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3285	10078;10079;10080	chr2:178764662;178764661;178764660	chr2:179629389;179629388;179629387
N2AB	3285	10078;10079;10080	chr2:178764662;178764661;178764660	chr2:179629389;179629388;179629387
N2A	3285	10078;10079;10080	chr2:178764662;178764661;178764660	chr2:179629389;179629388;179629387
N2B	3239	9940;9941;9942	chr2:178764662;178764661;178764660	chr2:179629389;179629388;179629387
Novex-1	3239	9940;9941;9942	chr2:178764662;178764661;178764660	chr2:179629389;179629388;179629387
Novex-2	3239	9940;9941;9942	chr2:178764662;178764661;178764660	chr2:179629389;179629388;179629387
Novex-3	3285	10078;10079;10080	chr2:178764662;178764661;178764660	chr2:179629389;179629388;179629387

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-23
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1386
• 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
C/W	None	None	0.997	N	0.672	0.539	0.656562442728	gnomAD-4.0.0	6.84071E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15934E-05	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
C/A	0.8373	likely_pathogenic	0.8653	pathogenic	-1.593	Destabilizing	0.029	N	0.196	neutral	None	None	None	None	N
C/D	0.9875	likely_pathogenic	0.9958	pathogenic	-0.38	Destabilizing	0.974	D	0.678	prob.neutral	None	None	None	None	N
C/E	0.9883	likely_pathogenic	0.9951	pathogenic	-0.177	Destabilizing	0.974	D	0.666	neutral	None	None	None	None	N
C/F	0.5798	likely_pathogenic	0.7461	pathogenic	-0.936	Destabilizing	0.934	D	0.659	neutral	N	0.411468943	None	None	N
C/G	0.5825	likely_pathogenic	0.7464	pathogenic	-1.959	Destabilizing	0.801	D	0.628	neutral	N	0.508314711	None	None	N
C/H	0.9156	likely_pathogenic	0.9589	pathogenic	-2.019	Highly Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
C/I	0.8067	likely_pathogenic	0.8236	pathogenic	-0.617	Destabilizing	0.728	D	0.533	neutral	None	None	None	None	N
C/K	0.9863	likely_pathogenic	0.995	pathogenic	-0.596	Destabilizing	0.974	D	0.648	neutral	None	None	None	None	N
C/L	0.8165	likely_pathogenic	0.8579	pathogenic	-0.617	Destabilizing	0.525	D	0.534	neutral	None	None	None	None	N
C/M	0.8783	likely_pathogenic	0.9062	pathogenic	0.325	Stabilizing	0.974	D	0.625	neutral	None	None	None	None	N
C/N	0.9169	likely_pathogenic	0.9601	pathogenic	-1.029	Destabilizing	0.991	D	0.709	prob.delet.	None	None	None	None	N
C/P	0.9972	likely_pathogenic	0.9983	pathogenic	-0.918	Destabilizing	0.974	D	0.69	prob.neutral	None	None	None	None	N
C/Q	0.9547	likely_pathogenic	0.9807	pathogenic	-0.636	Destabilizing	0.991	D	0.707	prob.neutral	None	None	None	None	N
C/R	0.9008	likely_pathogenic	0.968	pathogenic	-0.928	Destabilizing	0.966	D	0.704	prob.neutral	N	0.48385242	None	None	N
C/S	0.7467	likely_pathogenic	0.8464	pathogenic	-1.49	Destabilizing	0.669	D	0.537	neutral	N	0.498943183	None	None	N
C/T	0.812	likely_pathogenic	0.8437	pathogenic	-1.075	Destabilizing	0.842	D	0.539	neutral	None	None	None	None	N
C/V	0.6557	likely_pathogenic	0.6269	pathogenic	-0.918	Destabilizing	0.016	N	0.331	neutral	None	None	None	None	N
C/W	0.855	likely_pathogenic	0.9381	pathogenic	-1.109	Destabilizing	0.997	D	0.672	neutral	N	0.509293798	None	None	N
C/Y	0.6415	likely_pathogenic	0.8097	pathogenic	-0.987	Destabilizing	0.966	D	0.665	neutral	N	0.430267771	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.