TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8217	24874;24875;24876	chr2:178718457;178718456;178718455	chr2:179583184;179583183;179583182
N2AB	7900	23923;23924;23925	chr2:178718457;178718456;178718455	chr2:179583184;179583183;179583182
N2A	6973	21142;21143;21144	chr2:178718457;178718456;178718455	chr2:179583184;179583183;179583182
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-67
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1293
• 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/R	None	None	0.016	N	0.485	0.382	0.719995979321	gnomAD-4.0.0	1.59134E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85842E-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
C/A	0.5541	ambiguous	0.5523	ambiguous	-1.507	Destabilizing	0.38	N	0.387	neutral	None	None	None	None	N
C/D	0.8866	likely_pathogenic	0.8935	pathogenic	-0.133	Destabilizing	0.584	D	0.603	neutral	None	None	None	None	N
C/E	0.8929	likely_pathogenic	0.9021	pathogenic	-0.032	Destabilizing	0.037	N	0.483	neutral	None	None	None	None	N
C/F	0.2495	likely_benign	0.2638	benign	-1.037	Destabilizing	0.719	D	0.673	neutral	N	0.482107862	None	None	N
C/G	0.341	ambiguous	0.364	ambiguous	-1.806	Destabilizing	0.679	D	0.585	neutral	N	0.48979416	None	None	N
C/H	0.5789	likely_pathogenic	0.5904	pathogenic	-2.001	Highly Destabilizing	0.96	D	0.684	prob.neutral	None	None	None	None	N
C/I	0.4967	ambiguous	0.5112	ambiguous	-0.75	Destabilizing	0.932	D	0.627	neutral	None	None	None	None	N
C/K	0.8722	likely_pathogenic	0.8783	pathogenic	-0.644	Destabilizing	0.037	N	0.483	neutral	None	None	None	None	N
C/L	0.544	ambiguous	0.5707	pathogenic	-0.75	Destabilizing	0.737	D	0.545	neutral	None	None	None	None	N
C/M	0.691	likely_pathogenic	0.6971	pathogenic	-0.04	Destabilizing	0.993	D	0.658	neutral	None	None	None	None	N
C/N	0.6628	likely_pathogenic	0.6869	pathogenic	-0.643	Destabilizing	0.872	D	0.635	neutral	None	None	None	None	N
C/P	0.9872	likely_pathogenic	0.9871	pathogenic	-0.975	Destabilizing	0.932	D	0.68	prob.neutral	None	None	None	None	N
C/Q	0.7308	likely_pathogenic	0.7409	pathogenic	-0.539	Destabilizing	0.872	D	0.65	neutral	None	None	None	None	N
C/R	0.5901	likely_pathogenic	0.6017	pathogenic	-0.678	Destabilizing	0.016	N	0.485	neutral	N	0.5081611	None	None	N
C/S	0.4099	ambiguous	0.4179	ambiguous	-1.162	Destabilizing	0.077	N	0.381	neutral	D	0.523071837	None	None	N
C/T	0.5367	ambiguous	0.5435	ambiguous	-0.872	Destabilizing	0.584	D	0.565	neutral	None	None	None	None	N
C/V	0.4542	ambiguous	0.4527	ambiguous	-0.975	Destabilizing	0.737	D	0.567	neutral	None	None	None	None	N
C/W	0.5964	likely_pathogenic	0.5969	pathogenic	-1.064	Destabilizing	0.993	D	0.645	neutral	N	0.490808118	None	None	N
C/Y	0.2904	likely_benign	0.3113	benign	-0.987	Destabilizing	0.064	N	0.47	neutral	N	0.415690869	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.