TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30242	90949;90950;90951	chr2:178552176;178552175;178552174	chr2:179416903;179416902;179416901
N2AB	28601	86026;86027;86028	chr2:178552176;178552175;178552174	chr2:179416903;179416902;179416901
N2A	27674	83245;83246;83247	chr2:178552176;178552175;178552174	chr2:179416903;179416902;179416901
N2B	21177	63754;63755;63756	chr2:178552176;178552175;178552174	chr2:179416903;179416902;179416901
Novex-1	21302	64129;64130;64131	chr2:178552176;178552175;178552174	chr2:179416903;179416902;179416901
Novex-2	21369	64330;64331;64332	chr2:178552176;178552175;178552174	chr2:179416903;179416902;179416901
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: Fn3-108
• Domain position: 19
• Structural Position: 20
• Q(SASA): 0.0499
• 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/F	rs756607075	-1.664	0.171	N	0.829	0.337	0.753651663445	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
V/F	rs756607075	-1.664	0.171	N	0.829	0.337	0.753651663445	gnomAD-4.0.0	4.77389E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57486E-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	0.2113	likely_benign	0.2149	benign	-2.049	Highly Destabilizing	None	N	0.261	neutral	N	0.515307998	None	None	N
V/C	0.6776	likely_pathogenic	0.6865	pathogenic	-1.565	Destabilizing	0.356	N	0.801	deleterious	None	None	None	None	N
V/D	0.9878	likely_pathogenic	0.9823	pathogenic	-3.107	Highly Destabilizing	0.171	N	0.816	deleterious	D	0.543615356	None	None	N
V/E	0.9754	likely_pathogenic	0.9666	pathogenic	-2.774	Highly Destabilizing	0.072	N	0.78	deleterious	None	None	None	None	N
V/F	0.5788	likely_pathogenic	0.5015	ambiguous	-1.184	Destabilizing	0.171	N	0.829	deleterious	N	0.501580268	None	None	N
V/G	0.596	likely_pathogenic	0.5763	pathogenic	-2.682	Highly Destabilizing	0.029	N	0.762	deleterious	D	0.542601398	None	None	N
V/H	0.9905	likely_pathogenic	0.9858	pathogenic	-2.714	Highly Destabilizing	0.864	D	0.797	deleterious	None	None	None	None	N
V/I	0.0844	likely_benign	0.0799	benign	-0.215	Destabilizing	None	N	0.205	neutral	N	0.462108231	None	None	N
V/K	0.9873	likely_pathogenic	0.981	pathogenic	-1.752	Destabilizing	0.072	N	0.781	deleterious	None	None	None	None	N
V/L	0.2226	likely_benign	0.2015	benign	-0.215	Destabilizing	0.002	N	0.478	neutral	N	0.496369946	None	None	N
V/M	0.2253	likely_benign	0.1911	benign	-0.467	Destabilizing	0.007	N	0.472	neutral	None	None	None	None	N
V/N	0.9476	likely_pathogenic	0.931	pathogenic	-2.489	Highly Destabilizing	0.356	N	0.825	deleterious	None	None	None	None	N
V/P	0.9893	likely_pathogenic	0.9849	pathogenic	-0.806	Destabilizing	0.214	N	0.817	deleterious	None	None	None	None	N
V/Q	0.9666	likely_pathogenic	0.953	pathogenic	-2.087	Highly Destabilizing	0.356	N	0.82	deleterious	None	None	None	None	N
V/R	0.9754	likely_pathogenic	0.9648	pathogenic	-1.964	Destabilizing	0.214	N	0.823	deleterious	None	None	None	None	N
V/S	0.6467	likely_pathogenic	0.6325	pathogenic	-3.0	Highly Destabilizing	0.038	N	0.74	deleterious	None	None	None	None	N
V/T	0.5061	ambiguous	0.4857	ambiguous	-2.491	Highly Destabilizing	0.038	N	0.629	neutral	None	None	None	None	N
V/W	0.9925	likely_pathogenic	0.9889	pathogenic	-1.786	Destabilizing	0.864	D	0.779	deleterious	None	None	None	None	N
V/Y	0.954	likely_pathogenic	0.9355	pathogenic	-1.381	Destabilizing	0.356	N	0.833	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.