TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35661	107206;107207;107208	chr2:178528770;178528769;178528768	chr2:179393497;179393496;179393495
N2AB	34020	102283;102284;102285	chr2:178528770;178528769;178528768	chr2:179393497;179393496;179393495
N2A	33093	99502;99503;99504	chr2:178528770;178528769;178528768	chr2:179393497;179393496;179393495
N2B	26596	80011;80012;80013	chr2:178528770;178528769;178528768	chr2:179393497;179393496;179393495
Novex-1	26721	80386;80387;80388	chr2:178528770;178528769;178528768	chr2:179393497;179393496;179393495
Novex-2	26788	80587;80588;80589	chr2:178528770;178528769;178528768	chr2:179393497;179393496;179393495
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-167
• Domain position: 55
• Structural Position: 137
• Q(SASA): 0.1892
• 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
T/I	rs747649004	0.175	0.967	N	0.659	0.501	0.510172456258	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	9.34E-05	0	0
T/I	rs747649004	0.175	0.967	N	0.659	0.501	0.510172456258	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.43E-05	0	0	0	0
T/I	rs747649004	0.175	0.967	N	0.659	0.501	0.510172456258	gnomAD-4.0.0	6.57462E-06	None	None	None	None	N	None	0	0	None	0	0	None	9.43396E-05	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
T/A	0.1878	likely_benign	0.1888	benign	-1.346	Destabilizing	0.025	N	0.489	neutral	N	0.482692226	None	None	N
T/C	0.7461	likely_pathogenic	0.7752	pathogenic	-1.217	Destabilizing	0.997	D	0.684	prob.neutral	None	None	None	None	N
T/D	0.7108	likely_pathogenic	0.7384	pathogenic	-1.81	Destabilizing	0.95	D	0.599	neutral	None	None	None	None	N
T/E	0.5257	ambiguous	0.5527	ambiguous	-1.619	Destabilizing	0.975	D	0.595	neutral	None	None	None	None	N
T/F	0.4	ambiguous	0.4275	ambiguous	-1.085	Destabilizing	0.987	D	0.746	deleterious	None	None	None	None	N
T/G	0.6105	likely_pathogenic	0.601	pathogenic	-1.737	Destabilizing	0.845	D	0.575	neutral	None	None	None	None	N
T/H	0.4471	ambiguous	0.4677	ambiguous	-1.814	Destabilizing	0.997	D	0.742	deleterious	None	None	None	None	N
T/I	0.2678	likely_benign	0.2898	benign	-0.323	Destabilizing	0.967	D	0.659	neutral	N	0.483732376	None	None	N
T/K	0.3763	ambiguous	0.406	ambiguous	-0.736	Destabilizing	0.975	D	0.619	neutral	None	None	None	None	N
T/L	0.1961	likely_benign	0.2009	benign	-0.323	Destabilizing	0.845	D	0.555	neutral	None	None	None	None	N
T/M	0.1341	likely_benign	0.1359	benign	-0.332	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
T/N	0.2536	likely_benign	0.2626	benign	-1.44	Destabilizing	0.204	N	0.438	neutral	N	0.46462654	None	None	N
T/P	0.598	likely_pathogenic	0.6773	pathogenic	-0.634	Destabilizing	0.983	D	0.662	neutral	N	0.483732376	None	None	N
T/Q	0.4131	ambiguous	0.4129	ambiguous	-1.286	Destabilizing	0.987	D	0.669	neutral	None	None	None	None	N
T/R	0.3415	ambiguous	0.3693	ambiguous	-0.849	Destabilizing	0.987	D	0.662	neutral	None	None	None	None	N
T/S	0.2268	likely_benign	0.2259	benign	-1.651	Destabilizing	0.805	D	0.539	neutral	N	0.480785284	None	None	N
T/V	0.2451	likely_benign	0.255	benign	-0.634	Destabilizing	0.845	D	0.539	neutral	None	None	None	None	N
T/W	0.788	likely_pathogenic	0.7942	pathogenic	-1.194	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
T/Y	0.4365	ambiguous	0.4487	ambiguous	-0.828	Destabilizing	0.996	D	0.751	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.