TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24927	75004;75005;75006	chr2:178571353;178571352;178571351	chr2:179436080;179436079;179436078
N2AB	23286	70081;70082;70083	chr2:178571353;178571352;178571351	chr2:179436080;179436079;179436078
N2A	22359	67300;67301;67302	chr2:178571353;178571352;178571351	chr2:179436080;179436079;179436078
N2B	15862	47809;47810;47811	chr2:178571353;178571352;178571351	chr2:179436080;179436079;179436078
Novex-1	15987	48184;48185;48186	chr2:178571353;178571352;178571351	chr2:179436080;179436079;179436078
Novex-2	16054	48385;48386;48387	chr2:178571353;178571352;178571351	chr2:179436080;179436079;179436078
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: Fn3-69
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1386
• 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/L	rs1468819805	-0.304	0.63	N	0.682	0.156	0.307332253619	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
V/L	rs1468819805	-0.304	0.63	N	0.682	0.156	0.307332253619	gnomAD-4.0.0	6.84347E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99611E-07	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	0.807	likely_pathogenic	0.8219	pathogenic	-2.424	Highly Destabilizing	0.892	D	0.679	prob.neutral	N	0.513443552	None	None	N
V/C	0.9309	likely_pathogenic	0.9399	pathogenic	-1.93	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
V/D	0.9974	likely_pathogenic	0.9971	pathogenic	-3.515	Highly Destabilizing	0.987	D	0.856	deleterious	None	None	None	None	N
V/E	0.9911	likely_pathogenic	0.9897	pathogenic	-3.188	Highly Destabilizing	0.967	D	0.808	deleterious	D	0.525813816	None	None	N
V/F	0.7449	likely_pathogenic	0.7878	pathogenic	-1.367	Destabilizing	0.987	D	0.696	prob.neutral	None	None	None	None	N
V/G	0.8846	likely_pathogenic	0.8889	pathogenic	-3.039	Highly Destabilizing	0.967	D	0.815	deleterious	D	0.525813816	None	None	N
V/H	0.9974	likely_pathogenic	0.9975	pathogenic	-2.965	Highly Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	N
V/I	0.0749	likely_benign	0.0762	benign	-0.628	Destabilizing	0.099	N	0.295	neutral	N	0.43640171	None	None	N
V/K	0.9945	likely_pathogenic	0.9935	pathogenic	-2.065	Highly Destabilizing	0.975	D	0.808	deleterious	None	None	None	None	N
V/L	0.341	ambiguous	0.3709	ambiguous	-0.628	Destabilizing	0.63	D	0.682	prob.neutral	N	0.410321469	None	None	N
V/M	0.5146	ambiguous	0.5667	pathogenic	-0.935	Destabilizing	0.987	D	0.657	neutral	None	None	None	None	N
V/N	0.9903	likely_pathogenic	0.9899	pathogenic	-2.789	Highly Destabilizing	0.987	D	0.855	deleterious	None	None	None	None	N
V/P	0.9931	likely_pathogenic	0.9921	pathogenic	-1.21	Destabilizing	0.073	N	0.681	prob.neutral	None	None	None	None	N
V/Q	0.9909	likely_pathogenic	0.9908	pathogenic	-2.414	Highly Destabilizing	0.987	D	0.832	deleterious	None	None	None	None	N
V/R	0.9911	likely_pathogenic	0.9902	pathogenic	-2.154	Highly Destabilizing	0.987	D	0.863	deleterious	None	None	None	None	N
V/S	0.9648	likely_pathogenic	0.968	pathogenic	-3.276	Highly Destabilizing	0.975	D	0.777	deleterious	None	None	None	None	N
V/T	0.9015	likely_pathogenic	0.9061	pathogenic	-2.789	Highly Destabilizing	0.916	D	0.653	neutral	None	None	None	None	N
V/W	0.9951	likely_pathogenic	0.9959	pathogenic	-1.97	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
V/Y	0.9767	likely_pathogenic	0.9798	pathogenic	-1.653	Destabilizing	0.996	D	0.69	prob.neutral	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.