TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10062	30409;30410;30411	chr2:178704186;178704185;178704184	chr2:179568913;179568912;179568911
N2AB	9745	29458;29459;29460	chr2:178704186;178704185;178704184	chr2:179568913;179568912;179568911
N2A	8818	26677;26678;26679	chr2:178704186;178704185;178704184	chr2:179568913;179568912;179568911
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-85
• Domain position: 74
• Structural Position: 158
• Q(SASA): 0.0672
• 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/F	rs2075481776	None	None	None	0.355	0.119	0.285698343383	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.54E-05	0	0	0	None	0	0	0	0	0
Y/F	rs2075481776	None	None	None	0.355	0.119	0.285698343383	gnomAD-4.0.0	6.56883E-06	None	None	None	None	N	None	0	6.54279E-05	None	0	0	None	0	0	0	0	0
Y/H	None	None	None	None	0.354	0.183	0.137902524267	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	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
Y/A	0.5999	likely_pathogenic	0.6054	pathogenic	-2.423	Highly Destabilizing	0.081	N	0.716	prob.delet.	None	None	None	None	N
Y/C	0.242	likely_benign	0.256	benign	-1.376	Destabilizing	0.002	N	0.614	neutral	None	None	None	None	N
Y/D	0.5809	likely_pathogenic	0.55	ambiguous	-1.901	Destabilizing	0.317	N	0.811	deleterious	None	None	None	None	N
Y/E	0.7613	likely_pathogenic	0.7488	pathogenic	-1.761	Destabilizing	0.235	N	0.775	deleterious	None	None	None	None	N
Y/F	0.1257	likely_benign	0.1455	benign	-0.971	Destabilizing	None	N	0.355	neutral	None	None	None	None	N
Y/G	0.6343	likely_pathogenic	0.631	pathogenic	-2.779	Highly Destabilizing	0.149	N	0.776	deleterious	None	None	None	None	N
Y/H	0.1267	likely_benign	0.1055	benign	-1.27	Destabilizing	None	N	0.354	neutral	None	None	None	None	N
Y/I	0.5729	likely_pathogenic	0.6219	pathogenic	-1.298	Destabilizing	0.081	N	0.713	prob.delet.	None	None	None	None	N
Y/K	0.6724	likely_pathogenic	0.6629	pathogenic	-1.744	Destabilizing	0.38	N	0.776	deleterious	None	None	None	None	N
Y/L	0.4522	ambiguous	0.4907	ambiguous	-1.298	Destabilizing	0.001	N	0.465	neutral	None	None	None	None	N
Y/M	0.6687	likely_pathogenic	0.7015	pathogenic	-1.04	Destabilizing	0.38	N	0.772	deleterious	None	None	None	None	N
Y/N	0.2668	likely_benign	0.2553	benign	-2.312	Highly Destabilizing	0.188	N	0.781	deleterious	None	None	None	None	N
Y/P	0.9682	likely_pathogenic	0.9624	pathogenic	-1.676	Destabilizing	0.555	D	0.829	deleterious	None	None	None	None	N
Y/Q	0.558	ambiguous	0.553	ambiguous	-2.125	Highly Destabilizing	0.38	N	0.781	deleterious	None	None	None	None	N
Y/R	0.4798	ambiguous	0.4677	ambiguous	-1.465	Destabilizing	0.38	N	0.796	deleterious	None	None	None	None	N
Y/S	0.4267	ambiguous	0.4166	ambiguous	-2.73	Highly Destabilizing	0.117	N	0.751	deleterious	None	None	None	None	N
Y/T	0.6124	likely_pathogenic	0.6243	pathogenic	-2.48	Highly Destabilizing	0.149	N	0.771	deleterious	None	None	None	None	N
Y/V	0.4701	ambiguous	0.4981	ambiguous	-1.676	Destabilizing	0.081	N	0.699	prob.neutral	None	None	None	None	N
Y/W	0.4363	ambiguous	0.4301	ambiguous	-0.501	Destabilizing	0.935	D	0.669	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.