TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27183	81772;81773;81774	chr2:178564585;178564584;178564583	chr2:179429312;179429311;179429310
N2AB	25542	76849;76850;76851	chr2:178564585;178564584;178564583	chr2:179429312;179429311;179429310
N2A	24615	74068;74069;74070	chr2:178564585;178564584;178564583	chr2:179429312;179429311;179429310
N2B	18118	54577;54578;54579	chr2:178564585;178564584;178564583	chr2:179429312;179429311;179429310
Novex-1	18243	54952;54953;54954	chr2:178564585;178564584;178564583	chr2:179429312;179429311;179429310
Novex-2	18310	55153;55154;55155	chr2:178564585;178564584;178564583	chr2:179429312;179429311;179429310
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-86
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2592
• 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
T/I	rs1559331817	None	0.994	D	0.761	0.477	0.684252380218	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
T/I	rs1559331817	None	0.994	D	0.761	0.477	0.684252380218	gnomAD-4.0.0	1.59203E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85901E-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
T/A	0.2895	likely_benign	0.2548	benign	-0.761	Destabilizing	0.825	D	0.461	neutral	N	0.48499695	None	None	I
T/C	0.6924	likely_pathogenic	0.6669	pathogenic	-0.796	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
T/D	0.6474	likely_pathogenic	0.6324	pathogenic	-1.511	Destabilizing	0.991	D	0.678	prob.neutral	None	None	None	None	I
T/E	0.7458	likely_pathogenic	0.7085	pathogenic	-1.453	Destabilizing	0.991	D	0.683	prob.neutral	None	None	None	None	I
T/F	0.7297	likely_pathogenic	0.6922	pathogenic	-0.792	Destabilizing	0.995	D	0.774	deleterious	None	None	None	None	I
T/G	0.3041	likely_benign	0.3034	benign	-1.058	Destabilizing	0.938	D	0.595	neutral	None	None	None	None	I
T/H	0.5065	ambiguous	0.4832	ambiguous	-1.432	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
T/I	0.8449	likely_pathogenic	0.8012	pathogenic	-0.047	Destabilizing	0.994	D	0.761	deleterious	D	0.525106254	None	None	I
T/K	0.4874	ambiguous	0.4348	ambiguous	-0.922	Destabilizing	0.988	D	0.685	prob.neutral	D	0.525218347	None	None	I
T/L	0.3809	ambiguous	0.3311	benign	-0.047	Destabilizing	0.968	D	0.59	neutral	None	None	None	None	I
T/M	0.2686	likely_benign	0.2325	benign	0.225	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
T/N	0.2008	likely_benign	0.1904	benign	-1.25	Destabilizing	0.991	D	0.679	prob.neutral	None	None	None	None	I
T/P	0.8452	likely_pathogenic	0.8204	pathogenic	-0.253	Destabilizing	0.994	D	0.757	deleterious	D	0.543210509	None	None	I
T/Q	0.4724	ambiguous	0.4374	ambiguous	-1.38	Destabilizing	0.991	D	0.745	deleterious	None	None	None	None	I
T/R	0.4823	ambiguous	0.417	ambiguous	-0.741	Destabilizing	0.988	D	0.747	deleterious	N	0.483248977	None	None	I
T/S	0.1325	likely_benign	0.124	benign	-1.333	Destabilizing	0.234	N	0.346	neutral	N	0.496124804	None	None	I
T/V	0.6949	likely_pathogenic	0.6444	pathogenic	-0.253	Destabilizing	0.968	D	0.539	neutral	None	None	None	None	I
T/W	0.9123	likely_pathogenic	0.8957	pathogenic	-0.866	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
T/Y	0.7072	likely_pathogenic	0.671	pathogenic	-0.537	Destabilizing	0.998	D	0.773	deleterious	None	None	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.