TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22903	68932;68933;68934	chr2:178577719;178577718;178577717	chr2:179442446;179442445;179442444
N2AB	21262	64009;64010;64011	chr2:178577719;178577718;178577717	chr2:179442446;179442445;179442444
N2A	20335	61228;61229;61230	chr2:178577719;178577718;178577717	chr2:179442446;179442445;179442444
N2B	13838	41737;41738;41739	chr2:178577719;178577718;178577717	chr2:179442446;179442445;179442444
Novex-1	13963	42112;42113;42114	chr2:178577719;178577718;178577717	chr2:179442446;179442445;179442444
Novex-2	14030	42313;42314;42315	chr2:178577719;178577718;178577717	chr2:179442446;179442445;179442444
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: Fn3-54
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1347
• 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	rs754632693	0.101	0.773	N	0.532	0.177	0.577700112626	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	8.7E-05	None	0	0	None	0	None	0	0	0
V/I	rs754632693	0.101	0.773	N	0.532	0.177	0.577700112626	gnomAD-4.0.0	4.77643E-06	None	None	None	None	N	None	0	6.86059E-05	None	0	0	None	0	0	0	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	0.5833	likely_pathogenic	0.6029	pathogenic	-1.729	Destabilizing	0.63	D	0.644	neutral	D	0.525586493	None	None	N
V/C	0.9313	likely_pathogenic	0.9439	pathogenic	-1.518	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
V/D	0.9892	likely_pathogenic	0.9932	pathogenic	-1.863	Destabilizing	0.975	D	0.837	deleterious	None	None	None	None	N
V/E	0.9698	likely_pathogenic	0.9774	pathogenic	-1.603	Destabilizing	0.967	D	0.819	deleterious	D	0.541959969	None	None	N
V/F	0.774	likely_pathogenic	0.8218	pathogenic	-1.006	Destabilizing	0.987	D	0.762	deleterious	None	None	None	None	N
V/G	0.9071	likely_pathogenic	0.9306	pathogenic	-2.313	Highly Destabilizing	0.967	D	0.815	deleterious	D	0.560064224	None	None	N
V/H	0.9911	likely_pathogenic	0.9934	pathogenic	-2.171	Highly Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
V/I	0.0903	likely_benign	0.0931	benign	-0.092	Destabilizing	0.773	D	0.532	neutral	N	0.504341643	None	None	N
V/K	0.9828	likely_pathogenic	0.9876	pathogenic	-1.319	Destabilizing	0.975	D	0.822	deleterious	None	None	None	None	N
V/L	0.5341	ambiguous	0.5821	pathogenic	-0.092	Destabilizing	0.63	D	0.649	neutral	N	0.480697174	None	None	N
V/M	0.51	ambiguous	0.543	ambiguous	-0.345	Destabilizing	0.996	D	0.717	prob.delet.	None	None	None	None	N
V/N	0.9659	likely_pathogenic	0.9757	pathogenic	-1.709	Destabilizing	0.975	D	0.843	deleterious	None	None	None	None	N
V/P	0.9825	likely_pathogenic	0.9871	pathogenic	-0.609	Destabilizing	0.987	D	0.823	deleterious	None	None	None	None	N
V/Q	0.9715	likely_pathogenic	0.9774	pathogenic	-1.424	Destabilizing	0.987	D	0.839	deleterious	None	None	None	None	N
V/R	0.9736	likely_pathogenic	0.9803	pathogenic	-1.446	Destabilizing	0.975	D	0.838	deleterious	None	None	None	None	N
V/S	0.8832	likely_pathogenic	0.9023	pathogenic	-2.427	Highly Destabilizing	0.95	D	0.779	deleterious	None	None	None	None	N
V/T	0.7854	likely_pathogenic	0.8089	pathogenic	-1.986	Destabilizing	0.033	N	0.367	neutral	None	None	None	None	N
V/W	0.9967	likely_pathogenic	0.9977	pathogenic	-1.458	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
V/Y	0.9765	likely_pathogenic	0.9842	pathogenic	-1.03	Destabilizing	0.996	D	0.757	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.