TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33347	100264;100265;100266	chr2:178537070;178537069;178537068	chr2:179401797;179401796;179401795
N2AB	31706	95341;95342;95343	chr2:178537070;178537069;178537068	chr2:179401797;179401796;179401795
N2A	30779	92560;92561;92562	chr2:178537070;178537069;178537068	chr2:179401797;179401796;179401795
N2B	24282	73069;73070;73071	chr2:178537070;178537069;178537068	chr2:179401797;179401796;179401795
Novex-1	24407	73444;73445;73446	chr2:178537070;178537069;178537068	chr2:179401797;179401796;179401795
Novex-2	24474	73645;73646;73647	chr2:178537070;178537069;178537068	chr2:179401797;179401796;179401795
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-130
• Domain position: 58
• Structural Position: 83
• Q(SASA): 0.5931
• 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
S/P	rs1575319690	None	0.949	N	0.645	0.304	0.27479166964	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-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
S/A	0.104	likely_benign	0.1116	benign	-0.391	Destabilizing	0.034	N	0.153	neutral	N	0.442791751	None	None	I
S/C	0.2546	likely_benign	0.2661	benign	-0.404	Destabilizing	0.996	D	0.633	neutral	None	None	None	None	I
S/D	0.726	likely_pathogenic	0.7785	pathogenic	0.365	Stabilizing	0.961	D	0.523	neutral	None	None	None	None	I
S/E	0.7831	likely_pathogenic	0.8387	pathogenic	0.308	Stabilizing	0.875	D	0.505	neutral	None	None	None	None	I
S/F	0.5253	ambiguous	0.5522	ambiguous	-0.881	Destabilizing	0.858	D	0.653	neutral	None	None	None	None	I
S/G	0.145	likely_benign	0.1498	benign	-0.542	Destabilizing	0.775	D	0.457	neutral	None	None	None	None	I
S/H	0.6411	likely_pathogenic	0.6931	pathogenic	-0.91	Destabilizing	0.996	D	0.636	neutral	None	None	None	None	I
S/I	0.4438	ambiguous	0.4987	ambiguous	-0.118	Destabilizing	0.858	D	0.541	neutral	None	None	None	None	I
S/K	0.8876	likely_pathogenic	0.9183	pathogenic	-0.418	Destabilizing	0.875	D	0.511	neutral	None	None	None	None	I
S/L	0.2347	likely_benign	0.2435	benign	-0.118	Destabilizing	0.008	N	0.29	neutral	N	0.48144614	None	None	I
S/M	0.3707	ambiguous	0.4017	ambiguous	-0.133	Destabilizing	0.923	D	0.649	neutral	None	None	None	None	I
S/N	0.2486	likely_benign	0.2861	benign	-0.292	Destabilizing	0.987	D	0.553	neutral	None	None	None	None	I
S/P	0.2172	likely_benign	0.2238	benign	-0.178	Destabilizing	0.949	D	0.645	neutral	N	0.437327217	None	None	I
S/Q	0.69	likely_pathogenic	0.7457	pathogenic	-0.43	Destabilizing	0.987	D	0.576	neutral	None	None	None	None	I
S/R	0.8397	likely_pathogenic	0.8753	pathogenic	-0.255	Destabilizing	0.961	D	0.649	neutral	None	None	None	None	I
S/T	0.1308	likely_benign	0.1369	benign	-0.364	Destabilizing	0.722	D	0.478	neutral	N	0.399075473	None	None	I
S/V	0.3932	ambiguous	0.4427	ambiguous	-0.178	Destabilizing	0.633	D	0.515	neutral	None	None	None	None	I
S/W	0.6717	likely_pathogenic	0.7229	pathogenic	-0.915	Destabilizing	0.996	D	0.721	prob.delet.	None	None	None	None	I
S/Y	0.4579	ambiguous	0.5021	ambiguous	-0.609	Destabilizing	0.961	D	0.658	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.