TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35757	107494;107495;107496	chr2:178528382;178528381;178528380	chr2:179393109;179393108;179393107
N2AB	34116	102571;102572;102573	chr2:178528382;178528381;178528380	chr2:179393109;179393108;179393107
N2A	33189	99790;99791;99792	chr2:178528382;178528381;178528380	chr2:179393109;179393108;179393107
N2B	26692	80299;80300;80301	chr2:178528382;178528381;178528380	chr2:179393109;179393108;179393107
Novex-1	26817	80674;80675;80676	chr2:178528382;178528381;178528380	chr2:179393109;179393108;179393107
Novex-2	26884	80875;80876;80877	chr2:178528382;178528381;178528380	chr2:179393109;179393108;179393107
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-168
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1366
• 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
Y/C	rs932225386	None	1.0	N	0.763	0.359	0.385249989106	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.78469E-04
Y/C	rs932225386	None	1.0	N	0.763	0.359	0.385249989106	gnomAD-4.0.0	1.85893E-06	None	None	None	None	N	None	0	1.66656E-05	None	0	0	None	0	0	0	0	3.20205E-05
Y/H	rs2154130935	None	0.265	N	0.531	0.269	0.180583059064	gnomAD-4.0.0	2.40066E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	6.07533E-05	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
Y/A	0.8176	likely_pathogenic	0.762	pathogenic	-2.923	Highly Destabilizing	0.993	D	0.737	prob.delet.	None	None	None	None	N
Y/C	0.2451	likely_benign	0.226	benign	-2.064	Highly Destabilizing	1.0	D	0.763	deleterious	N	0.424328129	None	None	N
Y/D	0.8924	likely_pathogenic	0.8205	pathogenic	-2.642	Highly Destabilizing	0.997	D	0.817	deleterious	N	0.460403572	None	None	N
Y/E	0.9675	likely_pathogenic	0.943	pathogenic	-2.448	Highly Destabilizing	0.996	D	0.768	deleterious	None	None	None	None	N
Y/F	0.1158	likely_benign	0.1111	benign	-1.124	Destabilizing	0.98	D	0.676	prob.neutral	N	0.463691807	None	None	N
Y/G	0.8642	likely_pathogenic	0.8073	pathogenic	-3.354	Highly Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
Y/H	0.4305	ambiguous	0.363	ambiguous	-1.875	Destabilizing	0.265	N	0.531	neutral	N	0.393023787	None	None	N
Y/I	0.6572	likely_pathogenic	0.6023	pathogenic	-1.524	Destabilizing	0.991	D	0.771	deleterious	None	None	None	None	N
Y/K	0.9592	likely_pathogenic	0.9271	pathogenic	-2.111	Highly Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
Y/L	0.6493	likely_pathogenic	0.615	pathogenic	-1.524	Destabilizing	0.171	N	0.594	neutral	None	None	None	None	N
Y/M	0.8526	likely_pathogenic	0.8224	pathogenic	-1.407	Destabilizing	0.996	D	0.766	deleterious	None	None	None	None	N
Y/N	0.6326	likely_pathogenic	0.5269	ambiguous	-2.816	Highly Destabilizing	0.994	D	0.782	deleterious	N	0.447839707	None	None	N
Y/P	0.9849	likely_pathogenic	0.9775	pathogenic	-2.001	Highly Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
Y/Q	0.8997	likely_pathogenic	0.8462	pathogenic	-2.564	Highly Destabilizing	0.998	D	0.785	deleterious	None	None	None	None	N
Y/R	0.8797	likely_pathogenic	0.8122	pathogenic	-1.842	Destabilizing	0.996	D	0.783	deleterious	None	None	None	None	N
Y/S	0.543	ambiguous	0.4588	ambiguous	-3.33	Highly Destabilizing	0.997	D	0.771	deleterious	N	0.366317188	None	None	N
Y/T	0.7764	likely_pathogenic	0.7149	pathogenic	-3.009	Highly Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
Y/V	0.5719	likely_pathogenic	0.5204	ambiguous	-2.001	Highly Destabilizing	0.971	D	0.744	deleterious	None	None	None	None	N
Y/W	0.5969	likely_pathogenic	0.5902	pathogenic	-0.469	Destabilizing	1.0	D	0.749	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.