TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17445	52558;52559;52560	chr2:178608678;178608677;178608676	chr2:179473405;179473404;179473403
N2AB	15804	47635;47636;47637	chr2:178608678;178608677;178608676	chr2:179473405;179473404;179473403
N2A	14877	44854;44855;44856	chr2:178608678;178608677;178608676	chr2:179473405;179473404;179473403
N2B	8380	25363;25364;25365	chr2:178608678;178608677;178608676	chr2:179473405;179473404;179473403
Novex-1	8505	25738;25739;25740	chr2:178608678;178608677;178608676	chr2:179473405;179473404;179473403
Novex-2	8572	25939;25940;25941	chr2:178608678;178608677;178608676	chr2:179473405;179473404;179473403
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-14
• Domain position: 77
• Structural Position: 108
• Q(SASA): 0.0554
• 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	rs1323206460	-1.098	0.997	N	0.649	0.372	0.737662299136	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.97E-06	0
V/I	rs1323206460	-1.098	0.997	N	0.649	0.372	0.737662299136	gnomAD-4.0.0	1.91776E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.52013E-05	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	0.8638	likely_pathogenic	0.8844	pathogenic	-2.718	Highly Destabilizing	0.999	D	0.667	neutral	D	0.544250234	None	None	N
V/C	0.952	likely_pathogenic	0.9562	pathogenic	-2.156	Highly Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
V/D	0.9983	likely_pathogenic	0.9987	pathogenic	-3.469	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/E	0.9944	likely_pathogenic	0.9958	pathogenic	-3.17	Highly Destabilizing	1.0	D	0.88	deleterious	D	0.633894794	None	None	N
V/F	0.9596	likely_pathogenic	0.9566	pathogenic	-1.5	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/G	0.9083	likely_pathogenic	0.9289	pathogenic	-3.265	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.633894794	None	None	N
V/H	0.9988	likely_pathogenic	0.999	pathogenic	-2.968	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/I	0.1394	likely_benign	0.1293	benign	-1.096	Destabilizing	0.997	D	0.649	neutral	N	0.518575668	None	None	N
V/K	0.996	likely_pathogenic	0.9969	pathogenic	-2.199	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/L	0.7871	likely_pathogenic	0.7969	pathogenic	-1.096	Destabilizing	0.997	D	0.69	prob.neutral	N	0.521102642	None	None	N
V/M	0.8854	likely_pathogenic	0.8728	pathogenic	-1.429	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
V/N	0.9943	likely_pathogenic	0.9952	pathogenic	-2.847	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/P	0.9945	likely_pathogenic	0.996	pathogenic	-1.625	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/Q	0.9933	likely_pathogenic	0.9948	pathogenic	-2.515	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
V/R	0.9908	likely_pathogenic	0.9934	pathogenic	-2.203	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/S	0.9725	likely_pathogenic	0.9758	pathogenic	-3.321	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/T	0.9363	likely_pathogenic	0.9339	pathogenic	-2.884	Highly Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
V/W	0.9993	likely_pathogenic	0.9993	pathogenic	-1.973	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/Y	0.9947	likely_pathogenic	0.9951	pathogenic	-1.815	Destabilizing	1.0	D	0.829	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.