TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10000	30223;30224;30225	chr2:178704372;178704371;178704370	chr2:179569099;179569098;179569097
N2AB	9683	29272;29273;29274	chr2:178704372;178704371;178704370	chr2:179569099;179569098;179569097
N2A	8756	26491;26492;26493	chr2:178704372;178704371;178704370	chr2:179569099;179569098;179569097
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-85
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.2892
• 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/P	rs768379279	-1.533	0.989	None	0.56	0.557	0.865652480908	gnomAD-2.1.1	2.41E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	5.31E-05	0
L/P	rs768379279	-1.533	0.989	None	0.56	0.557	0.865652480908	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.54E-05	0	0	0	None	0	0	0	0	0
L/P	rs768379279	-1.533	0.989	None	0.56	0.557	0.865652480908	gnomAD-4.0.0	9.29481E-06	None	None	None	None	N	None	0	1.66633E-05	None	0	0	None	0	0	1.18665E-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	0.4103	ambiguous	0.4405	ambiguous	-2.149	Highly Destabilizing	0.525	D	0.374	neutral	None	None	None	None	N
L/C	0.5638	ambiguous	0.6147	pathogenic	-1.343	Destabilizing	0.998	D	0.455	neutral	None	None	None	None	N
L/D	0.9466	likely_pathogenic	0.9608	pathogenic	-1.917	Destabilizing	0.974	D	0.573	neutral	None	None	None	None	N
L/E	0.6845	likely_pathogenic	0.7303	pathogenic	-1.85	Destabilizing	0.974	D	0.581	neutral	None	None	None	None	N
L/F	0.2196	likely_benign	0.2619	benign	-1.414	Destabilizing	0.037	N	0.221	neutral	None	None	None	None	N
L/G	0.734	likely_pathogenic	0.791	pathogenic	-2.549	Highly Destabilizing	0.007	N	0.299	neutral	None	None	None	None	N
L/H	0.5069	ambiguous	0.5799	pathogenic	-1.811	Destabilizing	0.998	D	0.524	neutral	None	None	None	None	N
L/I	0.1347	likely_benign	0.1329	benign	-1.071	Destabilizing	0.016	N	0.209	neutral	None	None	None	None	N
L/K	0.525	ambiguous	0.5834	pathogenic	-1.592	Destabilizing	0.974	D	0.523	neutral	None	None	None	None	N
L/M	0.1402	likely_benign	0.153	benign	-0.85	Destabilizing	0.934	D	0.493	neutral	None	None	None	None	N
L/N	0.8186	likely_pathogenic	0.8647	pathogenic	-1.499	Destabilizing	0.974	D	0.571	neutral	None	None	None	None	N
L/P	0.9605	likely_pathogenic	0.956	pathogenic	-1.403	Destabilizing	0.989	D	0.56	neutral	None	None	None	None	N
L/Q	0.3104	likely_benign	0.3688	ambiguous	-1.617	Destabilizing	0.989	D	0.515	neutral	None	None	None	None	N
L/R	0.3908	ambiguous	0.4448	ambiguous	-1.02	Destabilizing	0.966	D	0.517	neutral	None	None	None	None	N
L/S	0.5737	likely_pathogenic	0.6279	pathogenic	-2.146	Highly Destabilizing	0.728	D	0.463	neutral	None	None	None	None	N
L/T	0.4571	ambiguous	0.5044	ambiguous	-1.962	Destabilizing	0.067	N	0.234	neutral	None	None	None	None	N
L/V	0.1103	likely_benign	0.1088	benign	-1.403	Destabilizing	0.012	N	0.154	neutral	None	None	None	None	N
L/W	0.5371	ambiguous	0.5899	pathogenic	-1.59	Destabilizing	0.998	D	0.485	neutral	None	None	None	None	N
L/Y	0.6031	likely_pathogenic	0.6614	pathogenic	-1.369	Destabilizing	0.904	D	0.505	neutral	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.