TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15732	47419;47420;47421	chr2:178618264;178618263;178618262	chr2:179482991;179482990;179482989
N2AB	14091	42496;42497;42498	chr2:178618264;178618263;178618262	chr2:179482991;179482990;179482989
N2A	13164	39715;39716;39717	chr2:178618264;178618263;178618262	chr2:179482991;179482990;179482989
N2B	6667	20224;20225;20226	chr2:178618264;178618263;178618262	chr2:179482991;179482990;179482989
Novex-1	6792	20599;20600;20601	chr2:178618264;178618263;178618262	chr2:179482991;179482990;179482989
Novex-2	6859	20800;20801;20802	chr2:178618264;178618263;178618262	chr2:179482991;179482990;179482989
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-1
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0745
• 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
V/M	rs747351553	-1.381	1.0	D	0.777	0.646	0.751926697435	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	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
V/A	0.8938	likely_pathogenic	0.9275	pathogenic	-2.485	Highly Destabilizing	0.999	D	0.613	neutral	D	0.742058982	None	None	N
V/C	0.9754	likely_pathogenic	0.9764	pathogenic	-1.902	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
V/D	0.9992	likely_pathogenic	0.999	pathogenic	-3.544	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/E	0.9971	likely_pathogenic	0.9966	pathogenic	-3.223	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.813827173	None	None	N
V/F	0.9682	likely_pathogenic	0.9763	pathogenic	-1.416	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/G	0.9454	likely_pathogenic	0.9474	pathogenic	-3.085	Highly Destabilizing	1.0	D	0.89	deleterious	D	0.813827173	None	None	N
V/H	0.9994	likely_pathogenic	0.9994	pathogenic	-2.953	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
V/I	0.1635	likely_benign	0.1612	benign	-0.729	Destabilizing	0.998	D	0.608	neutral	None	None	None	None	N
V/K	0.998	likely_pathogenic	0.9972	pathogenic	-2.112	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/L	0.8617	likely_pathogenic	0.8971	pathogenic	-0.729	Destabilizing	0.997	D	0.629	neutral	D	0.65757047	None	None	N
V/M	0.9344	likely_pathogenic	0.9487	pathogenic	-0.981	Destabilizing	1.0	D	0.777	deleterious	D	0.683176339	None	None	N
V/N	0.9971	likely_pathogenic	0.9968	pathogenic	-2.812	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/P	0.9976	likely_pathogenic	0.9977	pathogenic	-1.298	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
V/Q	0.9968	likely_pathogenic	0.9968	pathogenic	-2.459	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
V/R	0.9949	likely_pathogenic	0.9938	pathogenic	-2.165	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
V/S	0.9812	likely_pathogenic	0.9849	pathogenic	-3.296	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/T	0.9507	likely_pathogenic	0.9598	pathogenic	-2.821	Highly Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
V/W	0.9997	likely_pathogenic	0.9997	pathogenic	-1.995	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/Y	0.9974	likely_pathogenic	0.9975	pathogenic	-1.693	Destabilizing	1.0	D	0.82	deleterious	None	None	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.