TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14787	44584;44585;44586	chr2:178629366;178629365;178629364	chr2:179494093;179494092;179494091
N2AB	13146	39661;39662;39663	chr2:178629366;178629365;178629364	chr2:179494093;179494092;179494091
N2A	12219	36880;36881;36882	chr2:178629366;178629365;178629364	chr2:179494093;179494092;179494091
N2B	5722	17389;17390;17391	chr2:178629366;178629365;178629364	chr2:179494093;179494092;179494091
Novex-1	5847	17764;17765;17766	chr2:178629366;178629365;178629364	chr2:179494093;179494092;179494091
Novex-2	5914	17965;17966;17967	chr2:178629366;178629365;178629364	chr2:179494093;179494092;179494091
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-99
• Domain position: 23
• Structural Position: 35
• Q(SASA): 0.0728
• 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/F	None	None	1.0	D	0.801	0.447	0.5551182358	gnomAD-4.0.0	6.84568E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99803E-07	0	0
L/I	None	None	0.999	N	0.557	0.247	0.403752378121	gnomAD-4.0.0	1.36914E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.87329E-05	0	8.99803E-07	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	0.9531	likely_pathogenic	0.9611	pathogenic	-2.486	Highly Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
L/C	0.9567	likely_pathogenic	0.9674	pathogenic	-1.511	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/D	0.9978	likely_pathogenic	0.9987	pathogenic	-3.163	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/E	0.9929	likely_pathogenic	0.9954	pathogenic	-2.858	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/F	0.7192	likely_pathogenic	0.7792	pathogenic	-1.472	Destabilizing	1.0	D	0.801	deleterious	D	0.569413913	None	None	N
L/G	0.987	likely_pathogenic	0.99	pathogenic	-3.069	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/H	0.9845	likely_pathogenic	0.9918	pathogenic	-2.843	Highly Destabilizing	1.0	D	0.85	deleterious	D	0.690546217	None	None	N
L/I	0.2486	likely_benign	0.3263	benign	-0.741	Destabilizing	0.999	D	0.557	neutral	N	0.490660065	None	None	N
L/K	0.9863	likely_pathogenic	0.9917	pathogenic	-1.729	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
L/M	0.3859	ambiguous	0.4598	ambiguous	-0.839	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
L/N	0.9877	likely_pathogenic	0.9926	pathogenic	-2.367	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/P	0.9932	likely_pathogenic	0.9959	pathogenic	-1.313	Destabilizing	1.0	D	0.855	deleterious	D	0.690546217	None	None	N
L/Q	0.9807	likely_pathogenic	0.9886	pathogenic	-2.047	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/R	0.9771	likely_pathogenic	0.9856	pathogenic	-1.789	Destabilizing	1.0	D	0.855	deleterious	D	0.690546217	None	None	N
L/S	0.9893	likely_pathogenic	0.9933	pathogenic	-2.903	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/T	0.9125	likely_pathogenic	0.938	pathogenic	-2.446	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
L/V	0.3127	likely_benign	0.3714	ambiguous	-1.313	Destabilizing	0.999	D	0.547	neutral	N	0.473619222	None	None	N
L/W	0.9652	likely_pathogenic	0.9787	pathogenic	-1.956	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
L/Y	0.969	likely_pathogenic	0.9793	pathogenic	-1.678	Destabilizing	1.0	D	0.858	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.