TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7672	23239;23240;23241	chr2:178721005;178721004;178721003	chr2:179585732;179585731;179585730
N2AB	7355	22288;22289;22290	chr2:178721005;178721004;178721003	chr2:179585732;179585731;179585730
N2A	6428	19507;19508;19509	chr2:178721005;178721004;178721003	chr2:179585732;179585731;179585730
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-61
• Domain position: 65
• Structural Position: 145
• Q(SASA): 0.2167
• 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/C	rs1470201253	None	0.998	D	0.449	0.293	0.375861065471	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	2.61986E-04	0	0	0	None	0	0	0	0	0
S/C	rs1470201253	None	0.998	D	0.449	0.293	0.375861065471	gnomAD-4.0.0	2.62829E-05	None	None	None	None	N	None	0	2.61986E-04	None	0	0	None	0	0	0	0	0
S/N	None	None	None	N	0.212	0.193	0.132336055621	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	0.0877	likely_benign	0.0866	benign	-0.533	Destabilizing	0.014	N	0.297	neutral	None	None	None	None	N
S/C	0.139	likely_benign	0.144	benign	-0.393	Destabilizing	0.998	D	0.449	neutral	D	0.528115084	None	None	N
S/D	0.2071	likely_benign	0.2374	benign	-0.663	Destabilizing	0.001	N	0.124	neutral	None	None	None	None	N
S/E	0.342	ambiguous	0.4032	ambiguous	-0.734	Destabilizing	0.006	N	0.152	neutral	None	None	None	None	N
S/F	0.23	likely_benign	0.243	benign	-1.08	Destabilizing	0.996	D	0.445	neutral	None	None	None	None	N
S/G	0.0755	likely_benign	0.0742	benign	-0.677	Destabilizing	0.001	N	0.161	neutral	N	0.483073441	None	None	N
S/H	0.2436	likely_benign	0.2638	benign	-1.266	Destabilizing	0.053	N	0.27	neutral	None	None	None	None	N
S/I	0.1591	likely_benign	0.1529	benign	-0.272	Destabilizing	0.989	D	0.456	neutral	D	0.522650549	None	None	N
S/K	0.3549	ambiguous	0.411	ambiguous	-0.654	Destabilizing	0.975	D	0.32	neutral	None	None	None	None	N
S/L	0.118	likely_benign	0.1147	benign	-0.272	Destabilizing	0.943	D	0.437	neutral	None	None	None	None	N
S/M	0.1996	likely_benign	0.1981	benign	0.239	Stabilizing	0.999	D	0.452	neutral	None	None	None	None	N
S/N	0.0992	likely_benign	0.0998	benign	-0.532	Destabilizing	None	N	0.212	neutral	N	0.508873176	None	None	N
S/P	0.626	likely_pathogenic	0.678	pathogenic	-0.33	Destabilizing	0.62	D	0.463	neutral	None	None	None	None	N
S/Q	0.331	likely_benign	0.3729	ambiguous	-0.895	Destabilizing	0.751	D	0.395	neutral	None	None	None	None	N
S/R	0.2792	likely_benign	0.3227	benign	-0.358	Destabilizing	0.986	D	0.466	neutral	N	0.472048371	None	None	N
S/T	0.0738	likely_benign	0.0763	benign	-0.56	Destabilizing	None	N	0.199	neutral	N	0.441090746	None	None	N
S/V	0.1654	likely_benign	0.1629	benign	-0.33	Destabilizing	0.86	D	0.433	neutral	None	None	None	None	N
S/W	0.3666	ambiguous	0.405	ambiguous	-1.051	Destabilizing	1.0	D	0.476	neutral	None	None	None	None	N
S/Y	0.2162	likely_benign	0.2383	benign	-0.772	Destabilizing	0.964	D	0.449	neutral	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.