TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33251	99976;99977;99978	chr2:178537456;178537455;178537454	chr2:179402183;179402182;179402181
N2AB	31610	95053;95054;95055	chr2:178537456;178537455;178537454	chr2:179402183;179402182;179402181
N2A	30683	92272;92273;92274	chr2:178537456;178537455;178537454	chr2:179402183;179402182;179402181
N2B	24186	72781;72782;72783	chr2:178537456;178537455;178537454	chr2:179402183;179402182;179402181
Novex-1	24311	73156;73157;73158	chr2:178537456;178537455;178537454	chr2:179402183;179402182;179402181
Novex-2	24378	73357;73358;73359	chr2:178537456;178537455;178537454	chr2:179402183;179402182;179402181
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-157
• Domain position: 49
• Structural Position: 135
• Q(SASA): 0.2274
• 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	rs377456237	-1.51	1.0	N	0.679	0.524	None	gnomAD-2.1.1	7.16E-06	None	None	None	None	N	None	8.29E-05	0	None	0	0	None	0	None	0	0	0
Y/C	rs377456237	-1.51	1.0	N	0.679	0.524	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	4.78011E-04
Y/C	rs377456237	-1.51	1.0	N	0.679	0.524	None	gnomAD-4.0.0	4.33918E-06	None	None	None	None	N	None	5.34088E-05	0	None	0	0	None	0	0	1.6955E-06	0	1.60164E-05

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	0.9374	likely_pathogenic	0.9353	pathogenic	-2.768	Highly Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
Y/C	0.5982	likely_pathogenic	0.6358	pathogenic	-1.243	Destabilizing	1.0	D	0.679	prob.neutral	N	0.50975861	None	None	N
Y/D	0.9361	likely_pathogenic	0.9372	pathogenic	-2.82	Highly Destabilizing	1.0	D	0.716	prob.delet.	N	0.494287725	None	None	N
Y/E	0.9835	likely_pathogenic	0.9795	pathogenic	-2.731	Highly Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
Y/F	0.2312	likely_benign	0.2454	benign	-0.995	Destabilizing	0.998	D	0.467	neutral	N	0.477262189	None	None	N
Y/G	0.8754	likely_pathogenic	0.882	pathogenic	-3.053	Highly Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
Y/H	0.7781	likely_pathogenic	0.7813	pathogenic	-1.781	Destabilizing	1.0	D	0.68	prob.neutral	N	0.519935531	None	None	N
Y/I	0.9199	likely_pathogenic	0.918	pathogenic	-1.836	Destabilizing	0.998	D	0.702	prob.neutral	None	None	None	None	N
Y/K	0.9782	likely_pathogenic	0.9732	pathogenic	-1.612	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
Y/L	0.8514	likely_pathogenic	0.8588	pathogenic	-1.836	Destabilizing	0.994	D	0.641	neutral	None	None	None	None	N
Y/M	0.9489	likely_pathogenic	0.9428	pathogenic	-1.33	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
Y/N	0.8136	likely_pathogenic	0.8223	pathogenic	-1.942	Destabilizing	1.0	D	0.705	prob.neutral	N	0.459809792	None	None	N
Y/P	0.9962	likely_pathogenic	0.9963	pathogenic	-2.154	Highly Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
Y/Q	0.9623	likely_pathogenic	0.961	pathogenic	-1.909	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
Y/R	0.9259	likely_pathogenic	0.9198	pathogenic	-1.139	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
Y/S	0.7428	likely_pathogenic	0.7696	pathogenic	-2.216	Highly Destabilizing	1.0	D	0.695	prob.neutral	N	0.466197047	None	None	N
Y/T	0.9263	likely_pathogenic	0.9295	pathogenic	-2.054	Highly Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
Y/V	0.8542	likely_pathogenic	0.8557	pathogenic	-2.154	Highly Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
Y/W	0.8341	likely_pathogenic	0.8206	pathogenic	-0.678	Destabilizing	1.0	D	0.653	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.