TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4867	14824;14825;14826	chr2:178735847;178735846;178735845	chr2:179600574;179600573;179600572
N2AB	4550	13873;13874;13875	chr2:178735847;178735846;178735845	chr2:179600574;179600573;179600572
N2A	3623	11092;11093;11094	chr2:178735847;178735846;178735845	chr2:179600574;179600573;179600572
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: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-31
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0644
• Site annotation: disulfide
• 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/F	rs2081352465	None	1.0	D	0.887	0.676	0.851595499224	gnomAD-4.0.0	3.18258E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	5.71615E-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	0.8138	likely_pathogenic	0.7808	pathogenic	-1.713	Destabilizing	0.998	D	0.725	prob.delet.	None	None	disulfide	None	N
C/D	0.9987	likely_pathogenic	0.9984	pathogenic	-1.478	Destabilizing	1.0	D	0.879	deleterious	None	None	disulfide	None	N
C/E	0.9987	likely_pathogenic	0.9985	pathogenic	-1.24	Destabilizing	1.0	D	0.899	deleterious	None	None	disulfide	None	N
C/F	0.7812	likely_pathogenic	0.7495	pathogenic	-1.018	Destabilizing	1.0	D	0.887	deleterious	D	0.781319746	disulfide	None	N
C/G	0.708	likely_pathogenic	0.6667	pathogenic	-2.081	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.783992476	disulfide	None	N
C/H	0.9914	likely_pathogenic	0.9896	pathogenic	-2.228	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	disulfide	None	N
C/I	0.7849	likely_pathogenic	0.7713	pathogenic	-0.708	Destabilizing	1.0	D	0.809	deleterious	None	None	disulfide	None	N
C/K	0.9988	likely_pathogenic	0.9987	pathogenic	-1.159	Destabilizing	1.0	D	0.878	deleterious	None	None	disulfide	None	N
C/L	0.6953	likely_pathogenic	0.6693	pathogenic	-0.708	Destabilizing	0.999	D	0.77	deleterious	None	None	disulfide	None	N
C/M	0.9177	likely_pathogenic	0.9029	pathogenic	0.289	Stabilizing	1.0	D	0.832	deleterious	None	None	disulfide	None	N
C/N	0.9895	likely_pathogenic	0.9868	pathogenic	-1.772	Destabilizing	1.0	D	0.899	deleterious	None	None	disulfide	None	N
C/P	0.9977	likely_pathogenic	0.9974	pathogenic	-1.021	Destabilizing	1.0	D	0.899	deleterious	None	None	disulfide	None	N
C/Q	0.9942	likely_pathogenic	0.9927	pathogenic	-1.296	Destabilizing	1.0	D	0.908	deleterious	None	None	disulfide	None	N
C/R	0.9853	likely_pathogenic	0.9841	pathogenic	-1.547	Destabilizing	1.0	D	0.903	deleterious	D	0.783992476	disulfide	None	N
C/S	0.8846	likely_pathogenic	0.8658	pathogenic	-2.093	Highly Destabilizing	1.0	D	0.801	deleterious	D	0.750512016	disulfide	None	N
C/T	0.9402	likely_pathogenic	0.9301	pathogenic	-1.667	Destabilizing	1.0	D	0.813	deleterious	None	None	disulfide	None	N
C/V	0.6602	likely_pathogenic	0.6351	pathogenic	-1.021	Destabilizing	0.999	D	0.792	deleterious	None	None	disulfide	None	N
C/W	0.9755	likely_pathogenic	0.9739	pathogenic	-1.391	Destabilizing	1.0	D	0.863	deleterious	D	0.783992476	disulfide	None	N
C/Y	0.9365	likely_pathogenic	0.9282	pathogenic	-1.219	Destabilizing	1.0	D	0.898	deleterious	D	0.783992476	disulfide	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.