TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28728	86407;86408;86409	chr2:178559950;178559949;178559948	chr2:179424677;179424676;179424675
N2AB	27087	81484;81485;81486	chr2:178559950;178559949;178559948	chr2:179424677;179424676;179424675
N2A	26160	78703;78704;78705	chr2:178559950;178559949;178559948	chr2:179424677;179424676;179424675
N2B	19663	59212;59213;59214	chr2:178559950;178559949;178559948	chr2:179424677;179424676;179424675
Novex-1	19788	59587;59588;59589	chr2:178559950;178559949;178559948	chr2:179424677;179424676;179424675
Novex-2	19855	59788;59789;59790	chr2:178559950;178559949;178559948	chr2:179424677;179424676;179424675
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: Fn3-97
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.1908
• 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/L	rs759990422	-0.689	None	N	0.18	0.142	0.139678290688	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
V/L	rs759990422	-0.689	None	N	0.18	0.142	0.139678290688	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/L	rs759990422	-0.689	None	N	0.18	0.142	0.139678290688	gnomAD-4.0.0	2.47875E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.39037E-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	0.174	likely_benign	0.208	benign	-1.324	Destabilizing	0.024	N	0.392	neutral	N	0.514177421	None	None	I
V/C	0.4855	ambiguous	0.5513	ambiguous	-1.589	Destabilizing	0.864	D	0.54	neutral	None	None	None	None	I
V/D	0.4426	ambiguous	0.474	ambiguous	-1.288	Destabilizing	0.171	N	0.641	neutral	N	0.484230617	None	None	I
V/E	0.2795	likely_benign	0.2976	benign	-1.262	Destabilizing	0.038	N	0.576	neutral	None	None	None	None	I
V/F	0.1086	likely_benign	0.1277	benign	-1.173	Destabilizing	0.093	N	0.603	neutral	N	0.513350702	None	None	I
V/G	0.2668	likely_benign	0.3177	benign	-1.605	Destabilizing	0.055	N	0.633	neutral	N	0.483977128	None	None	I
V/H	0.4032	ambiguous	0.4724	ambiguous	-1.076	Destabilizing	0.676	D	0.62	neutral	None	None	None	None	I
V/I	0.0557	likely_benign	0.0594	benign	-0.642	Destabilizing	None	N	0.148	neutral	N	0.427366513	None	None	I
V/K	0.2915	likely_benign	0.3335	benign	-0.867	Destabilizing	0.038	N	0.578	neutral	None	None	None	None	I
V/L	0.0976	likely_benign	0.1146	benign	-0.642	Destabilizing	None	N	0.18	neutral	N	0.508750172	None	None	I
V/M	0.0801	likely_benign	0.0904	benign	-0.88	Destabilizing	0.12	N	0.563	neutral	None	None	None	None	I
V/N	0.2309	likely_benign	0.2695	benign	-0.836	Destabilizing	0.214	N	0.633	neutral	None	None	None	None	I
V/P	0.9272	likely_pathogenic	0.9424	pathogenic	-0.839	Destabilizing	0.356	N	0.6	neutral	None	None	None	None	I
V/Q	0.2408	likely_benign	0.2815	benign	-1.024	Destabilizing	0.002	N	0.396	neutral	None	None	None	None	I
V/R	0.2514	likely_benign	0.2858	benign	-0.524	Destabilizing	0.12	N	0.644	neutral	None	None	None	None	I
V/S	0.1867	likely_benign	0.2219	benign	-1.439	Destabilizing	0.072	N	0.571	neutral	None	None	None	None	I
V/T	0.1372	likely_benign	0.1638	benign	-1.301	Destabilizing	0.072	N	0.515	neutral	None	None	None	None	I
V/W	0.5982	likely_pathogenic	0.6715	pathogenic	-1.279	Destabilizing	0.864	D	0.65	neutral	None	None	None	None	I
V/Y	0.373	ambiguous	0.4038	ambiguous	-0.923	Destabilizing	0.356	N	0.593	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.