TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13867	41824;41825;41826	chr2:178635972;178635971;178635970	chr2:179500699;179500698;179500697
N2AB	12226	36901;36902;36903	chr2:178635972;178635971;178635970	chr2:179500699;179500698;179500697
N2A	11299	34120;34121;34122	chr2:178635972;178635971;178635970	chr2:179500699;179500698;179500697
N2B	4802	14629;14630;14631	chr2:178635972;178635971;178635970	chr2:179500699;179500698;179500697
Novex-1	4927	15004;15005;15006	chr2:178635972;178635971;178635970	chr2:179500699;179500698;179500697
Novex-2	4994	15205;15206;15207	chr2:178635972;178635971;178635970	chr2:179500699;179500698;179500697
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-88
• Domain position: 88
• Structural Position: 175
• Q(SASA): 0.7645
• 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
K/E	rs1406730478	0.464	0.41	N	0.525	0.218	0.151104730317	gnomAD-2.1.1	4.2E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.26E-06	0
K/E	rs1406730478	0.464	0.41	N	0.525	0.218	0.151104730317	gnomAD-4.0.0	2.0779E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.7244E-06	0	0
K/I	rs2060384934	None	0.908	N	0.706	0.279	0.322786055943	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/I	rs2060384934	None	0.908	N	0.706	0.279	0.322786055943	gnomAD-4.0.0	6.57609E-06	None	None	None	None	N	None	2.41359E-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
K/A	0.797	likely_pathogenic	0.8948	pathogenic	-0.188	Destabilizing	0.648	D	0.609	neutral	None	None	None	None	N
K/C	0.902	likely_pathogenic	0.9432	pathogenic	-0.378	Destabilizing	0.993	D	0.703	prob.delet.	None	None	None	None	N
K/D	0.8752	likely_pathogenic	0.9439	pathogenic	-0.039	Destabilizing	0.764	D	0.689	prob.delet.	None	None	None	None	N
K/E	0.4724	ambiguous	0.6621	pathogenic	0.041	Stabilizing	0.41	N	0.525	neutral	N	0.336089411	None	None	N
K/F	0.9634	likely_pathogenic	0.9838	pathogenic	0.062	Stabilizing	0.993	D	0.663	prob.neutral	None	None	None	None	N
K/G	0.9058	likely_pathogenic	0.9499	pathogenic	-0.515	Destabilizing	0.48	N	0.575	neutral	None	None	None	None	N
K/H	0.4093	ambiguous	0.5355	ambiguous	-0.807	Destabilizing	0.961	D	0.713	prob.delet.	None	None	None	None	N
K/I	0.772	likely_pathogenic	0.8823	pathogenic	0.634	Stabilizing	0.908	D	0.706	prob.delet.	N	0.35021237	None	None	N
K/L	0.7658	likely_pathogenic	0.8627	pathogenic	0.634	Stabilizing	0.866	D	0.579	neutral	None	None	None	None	N
K/M	0.6093	likely_pathogenic	0.7549	pathogenic	0.312	Stabilizing	0.993	D	0.727	deleterious	None	None	None	None	N
K/N	0.6397	likely_pathogenic	0.8318	pathogenic	-0.237	Destabilizing	0.01	N	0.309	neutral	N	0.330456452	None	None	N
K/P	0.992	likely_pathogenic	0.9947	pathogenic	0.391	Stabilizing	0.929	D	0.745	deleterious	None	None	None	None	N
K/Q	0.2716	likely_benign	0.3664	ambiguous	-0.302	Destabilizing	0.83	D	0.693	prob.delet.	N	0.335692043	None	None	N
K/R	0.1191	likely_benign	0.1368	benign	-0.484	Destabilizing	0.581	D	0.585	neutral	N	0.339998157	None	None	N
K/S	0.7327	likely_pathogenic	0.8651	pathogenic	-0.769	Destabilizing	0.48	N	0.514	neutral	None	None	None	None	N
K/T	0.3957	ambiguous	0.5611	ambiguous	-0.504	Destabilizing	0.709	D	0.695	prob.delet.	N	0.339822141	None	None	N
K/V	0.707	likely_pathogenic	0.83	pathogenic	0.391	Stabilizing	0.929	D	0.705	prob.delet.	None	None	None	None	N
K/W	0.9497	likely_pathogenic	0.9735	pathogenic	0.11	Stabilizing	0.993	D	0.675	prob.neutral	None	None	None	None	N
K/Y	0.889	likely_pathogenic	0.9464	pathogenic	0.399	Stabilizing	0.976	D	0.702	prob.delet.	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.