TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31868	95827;95828;95829	chr2:178545508;178545507;178545506	chr2:179410235;179410234;179410233
N2AB	30227	90904;90905;90906	chr2:178545508;178545507;178545506	chr2:179410235;179410234;179410233
N2A	29300	88123;88124;88125	chr2:178545508;178545507;178545506	chr2:179410235;179410234;179410233
N2B	22803	68632;68633;68634	chr2:178545508;178545507;178545506	chr2:179410235;179410234;179410233
Novex-1	22928	69007;69008;69009	chr2:178545508;178545507;178545506	chr2:179410235;179410234;179410233
Novex-2	22995	69208;69209;69210	chr2:178545508;178545507;178545506	chr2:179410235;179410234;179410233
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: Fn3-120
• Domain position: 62
• Structural Position: 91
• Q(SASA): 0.176
• 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/M	None	None	0.996	N	0.797	0.299	0.509053020717	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
L/Q	rs1559138758	None	0.996	N	0.817	0.516	0.78423951252	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.56E-05	None	0	None	0	0	0
L/Q	rs1559138758	None	0.996	N	0.817	0.516	0.78423951252	gnomAD-4.0.0	1.59163E-06	None	None	None	None	N	None	0	0	None	0	2.77285E-05	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	0.6798	likely_pathogenic	0.6905	pathogenic	-2.203	Highly Destabilizing	0.972	D	0.599	neutral	None	None	None	None	N
L/C	0.5258	ambiguous	0.5633	ambiguous	-1.565	Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
L/D	0.9811	likely_pathogenic	0.9788	pathogenic	-2.111	Highly Destabilizing	0.997	D	0.845	deleterious	None	None	None	None	N
L/E	0.848	likely_pathogenic	0.841	pathogenic	-1.925	Destabilizing	0.992	D	0.809	deleterious	None	None	None	None	N
L/F	0.1884	likely_benign	0.1742	benign	-1.29	Destabilizing	0.968	D	0.763	deleterious	None	None	None	None	N
L/G	0.9101	likely_pathogenic	0.9098	pathogenic	-2.664	Highly Destabilizing	0.983	D	0.76	deleterious	None	None	None	None	N
L/H	0.5799	likely_pathogenic	0.569	pathogenic	-1.71	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
L/I	0.1422	likely_benign	0.1379	benign	-0.899	Destabilizing	0.972	D	0.605	neutral	None	None	None	None	N
L/K	0.7093	likely_pathogenic	0.7167	pathogenic	-1.794	Destabilizing	0.992	D	0.753	deleterious	None	None	None	None	N
L/M	0.1203	likely_benign	0.1253	benign	-0.861	Destabilizing	0.996	D	0.797	deleterious	N	0.51775087	None	None	N
L/N	0.8808	likely_pathogenic	0.8799	pathogenic	-2.108	Highly Destabilizing	0.997	D	0.846	deleterious	None	None	None	None	N
L/P	0.9937	likely_pathogenic	0.9914	pathogenic	-1.313	Destabilizing	0.996	D	0.844	deleterious	N	0.495642012	None	None	N
L/Q	0.4305	ambiguous	0.432	ambiguous	-2.014	Highly Destabilizing	0.996	D	0.817	deleterious	N	0.518444303	None	None	N
L/R	0.6281	likely_pathogenic	0.6159	pathogenic	-1.426	Destabilizing	0.989	D	0.808	deleterious	N	0.495135033	None	None	N
L/S	0.8252	likely_pathogenic	0.8151	pathogenic	-2.771	Highly Destabilizing	0.992	D	0.735	prob.delet.	None	None	None	None	N
L/T	0.6973	likely_pathogenic	0.6828	pathogenic	-2.437	Highly Destabilizing	0.992	D	0.715	prob.delet.	None	None	None	None	N
L/V	0.1469	likely_benign	0.1424	benign	-1.313	Destabilizing	0.963	D	0.587	neutral	N	0.447423993	None	None	N
L/W	0.4665	ambiguous	0.4368	ambiguous	-1.478	Destabilizing	0.11	N	0.589	neutral	None	None	None	None	N
L/Y	0.4369	ambiguous	0.4484	ambiguous	-1.227	Destabilizing	0.968	D	0.761	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.