TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24156	72691;72692;72693	chr2:178573666;178573665;178573664	chr2:179438393;179438392;179438391
N2AB	22515	67768;67769;67770	chr2:178573666;178573665;178573664	chr2:179438393;179438392;179438391
N2A	21588	64987;64988;64989	chr2:178573666;178573665;178573664	chr2:179438393;179438392;179438391
N2B	15091	45496;45497;45498	chr2:178573666;178573665;178573664	chr2:179438393;179438392;179438391
Novex-1	15216	45871;45872;45873	chr2:178573666;178573665;178573664	chr2:179438393;179438392;179438391
Novex-2	15283	46072;46073;46074	chr2:178573666;178573665;178573664	chr2:179438393;179438392;179438391
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-63
• Domain position: 35
• Structural Position: 36
• Q(SASA): 0.3307
• 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
D/N	rs1709040632	None	0.22	N	0.496	0.149	0.159798565429	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/N	rs1709040632	None	0.22	N	0.496	0.149	0.159798565429	gnomAD-4.0.0	6.57592E-06	None	None	None	None	I	None	2.41336E-05	0	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
D/A	0.1256	likely_benign	0.1559	benign	-0.494	Destabilizing	0.124	N	0.517	neutral	N	0.450411157	None	None	I
D/C	0.4423	ambiguous	0.5564	ambiguous	-0.26	Destabilizing	0.968	D	0.71	prob.delet.	None	None	None	None	I
D/E	0.1053	likely_benign	0.1283	benign	-0.51	Destabilizing	None	N	0.091	neutral	N	0.397808823	None	None	I
D/F	0.4633	ambiguous	0.5422	ambiguous	-0.311	Destabilizing	0.89	D	0.657	neutral	None	None	None	None	I
D/G	0.1515	likely_benign	0.1853	benign	-0.755	Destabilizing	0.124	N	0.469	neutral	N	0.457011842	None	None	I
D/H	0.2027	likely_benign	0.2554	benign	-0.437	Destabilizing	0.667	D	0.587	neutral	N	0.488796187	None	None	I
D/I	0.2285	likely_benign	0.2847	benign	0.166	Stabilizing	0.726	D	0.651	neutral	None	None	None	None	I
D/K	0.3023	likely_benign	0.3714	ambiguous	-0.43	Destabilizing	0.157	N	0.461	neutral	None	None	None	None	I
D/L	0.2415	likely_benign	0.3096	benign	0.166	Stabilizing	0.567	D	0.547	neutral	None	None	None	None	I
D/M	0.4131	ambiguous	0.4981	ambiguous	0.394	Stabilizing	0.968	D	0.655	neutral	None	None	None	None	I
D/N	0.0898	likely_benign	0.1033	benign	-0.6	Destabilizing	0.22	N	0.496	neutral	N	0.46089751	None	None	I
D/P	0.8317	likely_pathogenic	0.8537	pathogenic	-0.031	Destabilizing	0.726	D	0.532	neutral	None	None	None	None	I
D/Q	0.2211	likely_benign	0.2839	benign	-0.524	Destabilizing	0.157	N	0.483	neutral	None	None	None	None	I
D/R	0.3315	likely_benign	0.4139	ambiguous	-0.189	Destabilizing	0.396	N	0.563	neutral	None	None	None	None	I
D/S	0.0817	likely_benign	0.0969	benign	-0.791	Destabilizing	0.005	N	0.179	neutral	None	None	None	None	I
D/T	0.1153	likely_benign	0.1425	benign	-0.6	Destabilizing	0.157	N	0.472	neutral	None	None	None	None	I
D/V	0.1492	likely_benign	0.189	benign	-0.031	Destabilizing	0.497	N	0.547	neutral	N	0.437769934	None	None	I
D/W	0.8157	likely_pathogenic	0.864	pathogenic	-0.187	Destabilizing	0.968	D	0.767	deleterious	None	None	None	None	I
D/Y	0.1867	likely_benign	0.237	benign	-0.119	Destabilizing	0.859	D	0.657	neutral	N	0.496607594	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.