TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24628	74107;74108;74109	chr2:178572250;178572249;178572248	chr2:179436977;179436976;179436975
N2AB	22987	69184;69185;69186	chr2:178572250;178572249;178572248	chr2:179436977;179436976;179436975
N2A	22060	66403;66404;66405	chr2:178572250;178572249;178572248	chr2:179436977;179436976;179436975
N2B	15563	46912;46913;46914	chr2:178572250;178572249;178572248	chr2:179436977;179436976;179436975
Novex-1	15688	47287;47288;47289	chr2:178572250;178572249;178572248	chr2:179436977;179436976;179436975
Novex-2	15755	47488;47489;47490	chr2:178572250;178572249;178572248	chr2:179436977;179436976;179436975
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-67
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.2111
• 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/A	rs1277357050	-1.515	0.998	N	0.472	0.363	0.626300511109	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/A	rs1277357050	-1.515	0.998	N	0.472	0.363	0.626300511109	gnomAD-4.0.0	1.59224E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43345E-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
V/A	0.7415	likely_pathogenic	0.6576	pathogenic	-1.657	Destabilizing	0.998	D	0.472	neutral	N	0.475246806	None	None	N
V/C	0.9381	likely_pathogenic	0.936	pathogenic	-1.866	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
V/D	0.9811	likely_pathogenic	0.9747	pathogenic	-1.889	Destabilizing	1.0	D	0.866	deleterious	N	0.50843035	None	None	N
V/E	0.9462	likely_pathogenic	0.9192	pathogenic	-1.846	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
V/F	0.7926	likely_pathogenic	0.7219	pathogenic	-1.44	Destabilizing	1.0	D	0.822	deleterious	N	0.494556057	None	None	N
V/G	0.8578	likely_pathogenic	0.8163	pathogenic	-1.986	Destabilizing	1.0	D	0.843	deleterious	N	0.512406822	None	None	N
V/H	0.9809	likely_pathogenic	0.9749	pathogenic	-1.489	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
V/I	0.1083	likely_benign	0.0956	benign	-0.828	Destabilizing	0.297	N	0.289	neutral	N	0.490140194	None	None	N
V/K	0.9306	likely_pathogenic	0.9155	pathogenic	-1.295	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
V/L	0.7935	likely_pathogenic	0.7163	pathogenic	-0.828	Destabilizing	0.867	D	0.399	neutral	N	0.478018283	None	None	N
V/M	0.5084	ambiguous	0.3984	ambiguous	-0.982	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
V/N	0.9261	likely_pathogenic	0.9014	pathogenic	-1.325	Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
V/P	0.9941	likely_pathogenic	0.9946	pathogenic	-1.073	Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
V/Q	0.9186	likely_pathogenic	0.8781	pathogenic	-1.493	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/R	0.9132	likely_pathogenic	0.8926	pathogenic	-0.873	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/S	0.8247	likely_pathogenic	0.7725	pathogenic	-1.918	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/T	0.5724	likely_pathogenic	0.5287	ambiguous	-1.756	Destabilizing	0.995	D	0.631	neutral	None	None	None	None	N
V/W	0.9943	likely_pathogenic	0.9924	pathogenic	-1.605	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
V/Y	0.9684	likely_pathogenic	0.9564	pathogenic	-1.263	Destabilizing	1.0	D	0.825	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.