TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28625	86098;86099;86100	chr2:178560259;178560258;178560257	chr2:179424986;179424985;179424984
N2AB	26984	81175;81176;81177	chr2:178560259;178560258;178560257	chr2:179424986;179424985;179424984
N2A	26057	78394;78395;78396	chr2:178560259;178560258;178560257	chr2:179424986;179424985;179424984
N2B	19560	58903;58904;58905	chr2:178560259;178560258;178560257	chr2:179424986;179424985;179424984
Novex-1	19685	59278;59279;59280	chr2:178560259;178560258;178560257	chr2:179424986;179424985;179424984
Novex-2	19752	59479;59480;59481	chr2:178560259;178560258;178560257	chr2:179424986;179424985;179424984
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-96
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0571
• 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/I	None	None	0.997	N	0.643	0.425	0.723563167763	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
V/A	0.6274	likely_pathogenic	0.5898	pathogenic	-2.599	Highly Destabilizing	0.999	D	0.663	neutral	D	0.561696153	None	None	N
V/C	0.9288	likely_pathogenic	0.9215	pathogenic	-1.852	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/D	0.9957	likely_pathogenic	0.9961	pathogenic	-3.457	Highly Destabilizing	1.0	D	0.886	deleterious	D	0.65316446	None	None	N
V/E	0.9896	likely_pathogenic	0.9907	pathogenic	-3.148	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/F	0.8788	likely_pathogenic	0.8938	pathogenic	-1.51	Destabilizing	1.0	D	0.828	deleterious	D	0.584408764	None	None	N
V/G	0.8022	likely_pathogenic	0.8035	pathogenic	-3.151	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.65316446	None	None	N
V/H	0.9971	likely_pathogenic	0.9974	pathogenic	-2.972	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/I	0.1078	likely_benign	0.108	benign	-0.963	Destabilizing	0.997	D	0.643	neutral	N	0.514804644	None	None	N
V/K	0.9929	likely_pathogenic	0.9946	pathogenic	-2.138	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/L	0.5323	ambiguous	0.5607	ambiguous	-0.963	Destabilizing	0.997	D	0.681	prob.neutral	N	0.517481791	None	None	N
V/M	0.7065	likely_pathogenic	0.7032	pathogenic	-1.23	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
V/N	0.9841	likely_pathogenic	0.9849	pathogenic	-2.837	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
V/P	0.9913	likely_pathogenic	0.9901	pathogenic	-1.496	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/Q	0.9883	likely_pathogenic	0.9895	pathogenic	-2.479	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
V/R	0.9835	likely_pathogenic	0.9864	pathogenic	-2.2	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
V/S	0.9186	likely_pathogenic	0.9093	pathogenic	-3.248	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
V/T	0.8341	likely_pathogenic	0.8143	pathogenic	-2.8	Highly Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
V/W	0.9982	likely_pathogenic	0.9984	pathogenic	-1.988	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/Y	0.9882	likely_pathogenic	0.9898	pathogenic	-1.788	Destabilizing	1.0	D	0.827	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.