TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13919	41980;41981;41982	chr2:178635569;178635568;178635567	chr2:179500296;179500295;179500294
N2AB	12278	37057;37058;37059	chr2:178635569;178635568;178635567	chr2:179500296;179500295;179500294
N2A	11351	34276;34277;34278	chr2:178635569;178635568;178635567	chr2:179500296;179500295;179500294
N2B	4854	14785;14786;14787	chr2:178635569;178635568;178635567	chr2:179500296;179500295;179500294
Novex-1	4979	15160;15161;15162	chr2:178635569;178635568;178635567	chr2:179500296;179500295;179500294
Novex-2	5046	15361;15362;15363	chr2:178635569;178635568;178635567	chr2:179500296;179500295;179500294
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-89
• Domain position: 44
• Structural Position: 111
• Q(SASA): 0.623
• 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
D/G	rs2060334191	None	0.457	N	0.539	0.195	0.185906805712	gnomAD-4.0.0	6.56463E-06	None	None	None	None	I	None	0	0	None	0	1.12816E-04	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
D/A	0.3256	likely_benign	0.351	ambiguous	0.02	Stabilizing	0.297	N	0.448	neutral	N	0.489326599	None	None	I
D/C	0.8616	likely_pathogenic	0.8944	pathogenic	-0.087	Destabilizing	0.989	D	0.759	deleterious	None	None	None	None	I
D/E	0.1732	likely_benign	0.1977	benign	-0.294	Destabilizing	0.003	N	0.381	neutral	N	0.446624253	None	None	I
D/F	0.8594	likely_pathogenic	0.8827	pathogenic	-0.14	Destabilizing	0.989	D	0.654	prob.neutral	None	None	None	None	I
D/G	0.314	likely_benign	0.32	benign	-0.073	Destabilizing	0.457	N	0.539	neutral	N	0.429527929	None	None	I
D/H	0.6016	likely_pathogenic	0.6131	pathogenic	0.436	Stabilizing	0.958	D	0.476	neutral	N	0.493859092	None	None	I
D/I	0.6907	likely_pathogenic	0.7382	pathogenic	0.194	Stabilizing	0.888	D	0.701	prob.delet.	None	None	None	None	I
D/K	0.6779	likely_pathogenic	0.6966	pathogenic	0.407	Stabilizing	0.359	N	0.523	neutral	None	None	None	None	I
D/L	0.6646	likely_pathogenic	0.7168	pathogenic	0.194	Stabilizing	0.797	D	0.725	deleterious	None	None	None	None	I
D/M	0.8474	likely_pathogenic	0.8955	pathogenic	0.045	Stabilizing	0.989	D	0.722	deleterious	None	None	None	None	I
D/N	0.1897	likely_benign	0.1958	benign	0.27	Stabilizing	0.025	N	0.398	neutral	N	0.449769997	None	None	I
D/P	0.7689	likely_pathogenic	0.787	pathogenic	0.154	Stabilizing	0.888	D	0.524	neutral	None	None	None	None	I
D/Q	0.5646	likely_pathogenic	0.5964	pathogenic	0.254	Stabilizing	0.662	D	0.587	neutral	None	None	None	None	I
D/R	0.7346	likely_pathogenic	0.7448	pathogenic	0.592	Stabilizing	0.797	D	0.641	neutral	None	None	None	None	I
D/S	0.2309	likely_benign	0.2429	benign	0.153	Stabilizing	0.359	N	0.51	neutral	None	None	None	None	I
D/T	0.4798	ambiguous	0.518	ambiguous	0.229	Stabilizing	0.797	D	0.535	neutral	None	None	None	None	I
D/V	0.5269	ambiguous	0.5638	ambiguous	0.154	Stabilizing	0.747	D	0.723	deleterious	N	0.432865354	None	None	I
D/W	0.9629	likely_pathogenic	0.9711	pathogenic	-0.124	Destabilizing	0.989	D	0.739	deleterious	None	None	None	None	I
D/Y	0.5655	likely_pathogenic	0.5707	pathogenic	0.076	Stabilizing	0.986	D	0.654	prob.neutral	N	0.493642758	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.