TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22115	66568;66569;66570	chr2:178582026;178582025;178582024	chr2:179446753;179446752;179446751
N2AB	20474	61645;61646;61647	chr2:178582026;178582025;178582024	chr2:179446753;179446752;179446751
N2A	19547	58864;58865;58866	chr2:178582026;178582025;178582024	chr2:179446753;179446752;179446751
N2B	13050	39373;39374;39375	chr2:178582026;178582025;178582024	chr2:179446753;179446752;179446751
Novex-1	13175	39748;39749;39750	chr2:178582026;178582025;178582024	chr2:179446753;179446752;179446751
Novex-2	13242	39949;39950;39951	chr2:178582026;178582025;178582024	chr2:179446753;179446752;179446751
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-48
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.19
• 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
L/F	rs371010572	None	0.317	N	0.461	0.049	0.180583059064	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14837E-04	0	None	0	0	None	0	None	0	0	0
L/F	rs371010572	None	0.317	N	0.461	0.049	0.180583059064	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
L/F	rs371010572	None	0.317	N	0.461	0.049	0.180583059064	gnomAD-4.0.0	3.84555E-06	None	None	None	None	I	None	5.07872E-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
L/A	0.3141	likely_benign	0.3407	ambiguous	-2.026	Highly Destabilizing	0.035	N	0.457	neutral	None	None	None	None	I
L/C	0.446	ambiguous	0.4739	ambiguous	-1.417	Destabilizing	0.824	D	0.513	neutral	None	None	None	None	I
L/D	0.9231	likely_pathogenic	0.9324	pathogenic	-1.488	Destabilizing	0.555	D	0.619	neutral	None	None	None	None	I
L/E	0.6621	likely_pathogenic	0.7035	pathogenic	-1.307	Destabilizing	0.555	D	0.607	neutral	None	None	None	None	I
L/F	0.136	likely_benign	0.1445	benign	-1.095	Destabilizing	0.317	N	0.461	neutral	N	0.410601975	None	None	I
L/G	0.6957	likely_pathogenic	0.7279	pathogenic	-2.535	Highly Destabilizing	0.555	D	0.612	neutral	None	None	None	None	I
L/H	0.4254	ambiguous	0.4112	ambiguous	-1.823	Destabilizing	0.935	D	0.631	neutral	None	None	None	None	I
L/I	0.0877	likely_benign	0.0913	benign	-0.602	Destabilizing	None	N	0.112	neutral	N	0.433729551	None	None	I
L/K	0.561	ambiguous	0.5835	pathogenic	-1.478	Destabilizing	0.555	D	0.581	neutral	None	None	None	None	I
L/M	0.1001	likely_benign	0.1068	benign	-0.587	Destabilizing	0.38	N	0.484	neutral	None	None	None	None	I
L/N	0.6168	likely_pathogenic	0.6562	pathogenic	-1.661	Destabilizing	0.791	D	0.65	neutral	None	None	None	None	I
L/P	0.973	likely_pathogenic	0.9713	pathogenic	-1.051	Destabilizing	0.791	D	0.622	neutral	None	None	None	None	I
L/Q	0.2967	likely_benign	0.2987	benign	-1.541	Destabilizing	0.791	D	0.603	neutral	None	None	None	None	I
L/R	0.5287	ambiguous	0.5153	ambiguous	-1.221	Destabilizing	0.555	D	0.607	neutral	None	None	None	None	I
L/S	0.473	ambiguous	0.4975	ambiguous	-2.451	Highly Destabilizing	0.117	N	0.577	neutral	N	0.475055769	None	None	I
L/T	0.3389	likely_benign	0.364	ambiguous	-2.115	Highly Destabilizing	0.081	N	0.478	neutral	None	None	None	None	I
L/V	0.0898	likely_benign	0.0974	benign	-1.051	Destabilizing	None	N	0.151	neutral	N	0.450656299	None	None	I
L/W	0.4448	ambiguous	0.4267	ambiguous	-1.349	Destabilizing	0.935	D	0.653	neutral	None	None	None	None	I
L/Y	0.3739	ambiguous	0.3783	ambiguous	-1.053	Destabilizing	0.555	D	0.516	neutral	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.