TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18312	55159;55160;55161	chr2:178602468;178602467;178602466	chr2:179467195;179467194;179467193
N2AB	16671	50236;50237;50238	chr2:178602468;178602467;178602466	chr2:179467195;179467194;179467193
N2A	15744	47455;47456;47457	chr2:178602468;178602467;178602466	chr2:179467195;179467194;179467193
N2B	9247	27964;27965;27966	chr2:178602468;178602467;178602466	chr2:179467195;179467194;179467193
Novex-1	9372	28339;28340;28341	chr2:178602468;178602467;178602466	chr2:179467195;179467194;179467193
Novex-2	9439	28540;28541;28542	chr2:178602468;178602467;178602466	chr2:179467195;179467194;179467193
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Fn3-21
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.0547
• 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
Q/R	rs754977491	-1.107	0.997	N	0.502	0.415	0.231231049324	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
Q/R	rs754977491	-1.107	0.997	N	0.502	0.415	0.231231049324	gnomAD-4.0.0	1.59458E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86325E-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
Q/A	0.408	ambiguous	0.4087	ambiguous	-1.08	Destabilizing	0.997	D	0.563	neutral	None	None	None	None	N
Q/C	0.7079	likely_pathogenic	0.6913	pathogenic	-0.593	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Q/D	0.9399	likely_pathogenic	0.9506	pathogenic	-1.903	Destabilizing	0.997	D	0.505	neutral	None	None	None	None	N
Q/E	0.2071	likely_benign	0.1864	benign	-1.644	Destabilizing	0.992	D	0.441	neutral	N	0.452160596	None	None	N
Q/F	0.9134	likely_pathogenic	0.9341	pathogenic	-0.56	Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
Q/G	0.6212	likely_pathogenic	0.6518	pathogenic	-1.517	Destabilizing	0.997	D	0.677	prob.neutral	None	None	None	None	N
Q/H	0.7209	likely_pathogenic	0.7398	pathogenic	-1.226	Destabilizing	0.999	D	0.704	prob.neutral	N	0.475173529	None	None	N
Q/I	0.7462	likely_pathogenic	0.7078	pathogenic	0.106	Stabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
Q/K	0.2339	likely_benign	0.1858	benign	-0.542	Destabilizing	0.997	D	0.503	neutral	N	0.395363164	None	None	N
Q/L	0.302	likely_benign	0.2474	benign	0.106	Stabilizing	0.997	D	0.677	prob.neutral	N	0.479693914	None	None	N
Q/M	0.4247	ambiguous	0.3972	ambiguous	0.298	Stabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
Q/N	0.81	likely_pathogenic	0.8371	pathogenic	-1.336	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
Q/P	0.959	likely_pathogenic	0.9619	pathogenic	-0.263	Destabilizing	0.999	D	0.749	deleterious	N	0.482208565	None	None	N
Q/R	0.2417	likely_benign	0.203	benign	-0.718	Destabilizing	0.997	D	0.502	neutral	N	0.368080562	None	None	N
Q/S	0.686	likely_pathogenic	0.7104	pathogenic	-1.565	Destabilizing	0.997	D	0.466	neutral	None	None	None	None	N
Q/T	0.6355	likely_pathogenic	0.5763	pathogenic	-1.12	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
Q/V	0.5451	ambiguous	0.4942	ambiguous	-0.263	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
Q/W	0.9055	likely_pathogenic	0.9099	pathogenic	-0.639	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Q/Y	0.8582	likely_pathogenic	0.8796	pathogenic	-0.252	Destabilizing	0.999	D	0.808	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.