TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20540	61843;61844;61845	chr2:178590107;178590106;178590105	chr2:179454834;179454833;179454832
N2AB	18899	56920;56921;56922	chr2:178590107;178590106;178590105	chr2:179454834;179454833;179454832
N2A	17972	54139;54140;54141	chr2:178590107;178590106;178590105	chr2:179454834;179454833;179454832
N2B	11475	34648;34649;34650	chr2:178590107;178590106;178590105	chr2:179454834;179454833;179454832
Novex-1	11600	35023;35024;35025	chr2:178590107;178590106;178590105	chr2:179454834;179454833;179454832
Novex-2	11667	35224;35225;35226	chr2:178590107;178590106;178590105	chr2:179454834;179454833;179454832
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: Ig-121
• Domain position: 62
• Structural Position: 145
• Q(SASA): 0.2837
• Predicted PPI site: I

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/G	None	None	0.324	N	0.439	0.198	0.667260656149	gnomAD-4.0.0	4.80129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.25001E-06	0	0
V/I	None	None	0.001	N	0.213	0.064	0.301122078929	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1615	likely_benign	0.1349	benign	-1.055	Destabilizing	0.165	N	0.331	neutral	N	0.468159917	None	None	I
V/C	0.614	likely_pathogenic	0.5569	ambiguous	-0.801	Destabilizing	0.981	D	0.359	neutral	None	None	None	None	I
V/D	0.2912	likely_benign	0.2697	benign	-0.776	Destabilizing	0.627	D	0.445	neutral	N	0.441666749	None	None	I
V/E	0.2031	likely_benign	0.2029	benign	-0.856	Destabilizing	0.241	N	0.424	neutral	None	None	None	None	I
V/F	0.1793	likely_benign	0.1644	benign	-1.044	Destabilizing	0.627	D	0.389	neutral	N	0.457078918	None	None	I
V/G	0.1837	likely_benign	0.1619	benign	-1.268	Destabilizing	0.324	N	0.439	neutral	N	0.469026708	None	None	I
V/H	0.4488	ambiguous	0.4151	ambiguous	-0.75	Destabilizing	0.981	D	0.429	neutral	None	None	None	None	I
V/I	0.0824	likely_benign	0.0734	benign	-0.613	Destabilizing	0.001	N	0.213	neutral	N	0.480859855	None	None	I
V/K	0.193	likely_benign	0.2106	benign	-0.896	Destabilizing	0.002	N	0.262	neutral	None	None	None	None	I
V/L	0.1294	likely_benign	0.1119	benign	-0.613	Destabilizing	0.001	N	0.153	neutral	N	0.468026631	None	None	I
V/M	0.1136	likely_benign	0.0998	benign	-0.436	Destabilizing	0.69	D	0.361	neutral	None	None	None	None	I
V/N	0.1518	likely_benign	0.1477	benign	-0.63	Destabilizing	0.69	D	0.44	neutral	None	None	None	None	I
V/P	0.8576	likely_pathogenic	0.8353	pathogenic	-0.724	Destabilizing	0.818	D	0.433	neutral	None	None	None	None	I
V/Q	0.1916	likely_benign	0.1837	benign	-0.889	Destabilizing	0.69	D	0.425	neutral	None	None	None	None	I
V/R	0.2188	likely_benign	0.2238	benign	-0.289	Destabilizing	0.527	D	0.446	neutral	None	None	None	None	I
V/S	0.1364	likely_benign	0.1301	benign	-1.073	Destabilizing	0.241	N	0.427	neutral	None	None	None	None	I
V/T	0.1109	likely_benign	0.1037	benign	-1.052	Destabilizing	0.004	N	0.145	neutral	None	None	None	None	I
V/W	0.8426	likely_pathogenic	0.7859	pathogenic	-1.127	Destabilizing	0.981	D	0.489	neutral	None	None	None	None	I
V/Y	0.5584	ambiguous	0.5053	ambiguous	-0.852	Destabilizing	0.818	D	0.375	neutral	None	None	None	None	I

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.