TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27677	83254;83255;83256	chr2:178563103;178563102;178563101	chr2:179427830;179427829;179427828
N2AB	26036	78331;78332;78333	chr2:178563103;178563102;178563101	chr2:179427830;179427829;179427828
N2A	25109	75550;75551;75552	chr2:178563103;178563102;178563101	chr2:179427830;179427829;179427828
N2B	18612	56059;56060;56061	chr2:178563103;178563102;178563101	chr2:179427830;179427829;179427828
Novex-1	18737	56434;56435;56436	chr2:178563103;178563102;178563101	chr2:179427830;179427829;179427828
Novex-2	18804	56635;56636;56637	chr2:178563103;178563102;178563101	chr2:179427830;179427829;179427828
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-141
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.242
• 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
L/I	rs1704290061	None	0.999	N	0.457	0.257	0.439551795455	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/I	rs1704290061	None	0.999	N	0.457	0.257	0.439551795455	gnomAD-4.0.0	6.57393E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47016E-05	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
L/A	0.9416	likely_pathogenic	0.9319	pathogenic	-1.327	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
L/C	0.9794	likely_pathogenic	0.9709	pathogenic	-0.907	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
L/D	0.9969	likely_pathogenic	0.9957	pathogenic	-0.476	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
L/E	0.9861	likely_pathogenic	0.9826	pathogenic	-0.497	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
L/F	0.8333	likely_pathogenic	0.7971	pathogenic	-0.943	Destabilizing	1.0	D	0.675	prob.neutral	N	0.51035395	None	None	N
L/G	0.986	likely_pathogenic	0.9811	pathogenic	-1.618	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
L/H	0.9865	likely_pathogenic	0.9774	pathogenic	-0.834	Destabilizing	1.0	D	0.793	deleterious	D	0.534245103	None	None	N
L/I	0.3075	likely_benign	0.316	benign	-0.626	Destabilizing	0.999	D	0.457	neutral	N	0.499616302	None	None	N
L/K	0.9712	likely_pathogenic	0.9599	pathogenic	-0.827	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
L/M	0.3648	ambiguous	0.3506	ambiguous	-0.566	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
L/N	0.9859	likely_pathogenic	0.9808	pathogenic	-0.595	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
L/P	0.9574	likely_pathogenic	0.9345	pathogenic	-0.826	Destabilizing	1.0	D	0.786	deleterious	N	0.511025513	None	None	N
L/Q	0.9726	likely_pathogenic	0.9592	pathogenic	-0.767	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
L/R	0.9646	likely_pathogenic	0.9475	pathogenic	-0.289	Destabilizing	1.0	D	0.774	deleterious	D	0.533991614	None	None	N
L/S	0.9902	likely_pathogenic	0.986	pathogenic	-1.223	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
L/T	0.9027	likely_pathogenic	0.8849	pathogenic	-1.121	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
L/V	0.4534	ambiguous	0.4494	ambiguous	-0.826	Destabilizing	0.999	D	0.506	neutral	N	0.512591995	None	None	N
L/W	0.9295	likely_pathogenic	0.8984	pathogenic	-0.963	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
L/Y	0.9691	likely_pathogenic	0.9561	pathogenic	-0.739	Destabilizing	1.0	D	0.763	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.