TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23888	71887;71888;71889	chr2:178574470;178574469;178574468	chr2:179439197;179439196;179439195
N2AB	22247	66964;66965;66966	chr2:178574470;178574469;178574468	chr2:179439197;179439196;179439195
N2A	21320	64183;64184;64185	chr2:178574470;178574469;178574468	chr2:179439197;179439196;179439195
N2B	14823	44692;44693;44694	chr2:178574470;178574469;178574468	chr2:179439197;179439196;179439195
Novex-1	14948	45067;45068;45069	chr2:178574470;178574469;178574468	chr2:179439197;179439196;179439195
Novex-2	15015	45268;45269;45270	chr2:178574470;178574469;178574468	chr2:179439197;179439196;179439195
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: Fn3-61
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1495
• 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
S/P	None	None	0.97	N	0.841	0.326	0.272205846399	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

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	0.0829	likely_benign	0.0893	benign	-0.795	Destabilizing	0.489	N	0.58	neutral	N	0.354228617	None	None	N
S/C	0.0745	likely_benign	0.0816	benign	-0.364	Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
S/D	0.8758	likely_pathogenic	0.8929	pathogenic	-0.418	Destabilizing	0.86	D	0.73	prob.delet.	None	None	None	None	N
S/E	0.905	likely_pathogenic	0.9292	pathogenic	-0.232	Destabilizing	0.86	D	0.721	prob.delet.	None	None	None	None	N
S/F	0.4837	ambiguous	0.5093	ambiguous	-0.842	Destabilizing	0.956	D	0.849	deleterious	None	None	None	None	N
S/G	0.1936	likely_benign	0.1837	benign	-1.18	Destabilizing	0.86	D	0.716	prob.delet.	None	None	None	None	N
S/H	0.802	likely_pathogenic	0.8355	pathogenic	-1.429	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
S/I	0.1711	likely_benign	0.1799	benign	0.182	Stabilizing	0.754	D	0.789	deleterious	None	None	None	None	N
S/K	0.9857	likely_pathogenic	0.9886	pathogenic	0.272	Stabilizing	0.86	D	0.713	prob.delet.	None	None	None	None	N
S/L	0.1622	likely_benign	0.1683	benign	0.182	Stabilizing	0.698	D	0.765	deleterious	N	0.38375373	None	None	N
S/M	0.2678	likely_benign	0.2818	benign	0.072	Stabilizing	0.978	D	0.831	deleterious	None	None	None	None	N
S/N	0.4323	ambiguous	0.4583	ambiguous	-0.344	Destabilizing	0.86	D	0.714	prob.delet.	None	None	None	None	N
S/P	0.8808	likely_pathogenic	0.8688	pathogenic	-0.11	Destabilizing	0.97	D	0.841	deleterious	N	0.481347353	None	None	N
S/Q	0.8984	likely_pathogenic	0.92	pathogenic	-0.12	Destabilizing	0.978	D	0.757	deleterious	None	None	None	None	N
S/R	0.9783	likely_pathogenic	0.9818	pathogenic	-0.153	Destabilizing	0.978	D	0.839	deleterious	None	None	None	None	N
S/T	0.0764	likely_benign	0.0848	benign	-0.174	Destabilizing	0.025	N	0.329	neutral	N	0.388975909	None	None	N
S/V	0.1419	likely_benign	0.1584	benign	-0.11	Destabilizing	0.019	N	0.625	neutral	None	None	None	None	N
S/W	0.7384	likely_pathogenic	0.7549	pathogenic	-0.946	Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	N
S/Y	0.4426	ambiguous	0.4774	ambiguous	-0.501	Destabilizing	0.978	D	0.849	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.