TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2999	9220;9221;9222	chr2:178768841;178768840;178768839	chr2:179633568;179633567;179633566
N2AB	2999	9220;9221;9222	chr2:178768841;178768840;178768839	chr2:179633568;179633567;179633566
N2A	2999	9220;9221;9222	chr2:178768841;178768840;178768839	chr2:179633568;179633567;179633566
N2B	2953	9082;9083;9084	chr2:178768841;178768840;178768839	chr2:179633568;179633567;179633566
Novex-1	2953	9082;9083;9084	chr2:178768841;178768840;178768839	chr2:179633568;179633567;179633566
Novex-2	2953	9082;9083;9084	chr2:178768841;178768840;178768839	chr2:179633568;179633567;179633566
Novex-3	2999	9220;9221;9222	chr2:178768841;178768840;178768839	chr2:179633568;179633567;179633566

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-20
• Domain position: 31
• Structural Position: 46
• Q(SASA): 0.1653
• 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	None	None	1.0	D	0.781	0.657	0.72559337781	gnomAD-4.0.0	1.59063E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-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	0.753	likely_pathogenic	0.7365	pathogenic	-2.74	Highly Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
Y/C	0.1825	likely_benign	0.2017	benign	-1.788	Destabilizing	1.0	D	0.781	deleterious	D	0.536410317	None	None	N
Y/D	0.9109	likely_pathogenic	0.9201	pathogenic	-2.882	Highly Destabilizing	1.0	D	0.756	deleterious	D	0.536589501	None	None	N
Y/E	0.9679	likely_pathogenic	0.9711	pathogenic	-2.729	Highly Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
Y/F	0.1304	likely_benign	0.1391	benign	-1.33	Destabilizing	0.999	D	0.633	neutral	N	0.506546319	None	None	N
Y/G	0.7039	likely_pathogenic	0.6663	pathogenic	-3.076	Highly Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
Y/H	0.425	ambiguous	0.4814	ambiguous	-1.604	Destabilizing	1.0	D	0.691	prob.neutral	D	0.536589501	None	None	N
Y/I	0.8633	likely_pathogenic	0.8738	pathogenic	-1.637	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
Y/K	0.9528	likely_pathogenic	0.9596	pathogenic	-2.13	Highly Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
Y/L	0.8295	likely_pathogenic	0.8076	pathogenic	-1.637	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	N
Y/M	0.8916	likely_pathogenic	0.896	pathogenic	-1.371	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
Y/N	0.6796	likely_pathogenic	0.7091	pathogenic	-2.776	Highly Destabilizing	1.0	D	0.749	deleterious	D	0.536589501	None	None	N
Y/P	0.9633	likely_pathogenic	0.9599	pathogenic	-2.014	Highly Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
Y/Q	0.8991	likely_pathogenic	0.9179	pathogenic	-2.619	Highly Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
Y/R	0.8782	likely_pathogenic	0.8969	pathogenic	-1.868	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
Y/S	0.4839	ambiguous	0.4818	ambiguous	-3.123	Highly Destabilizing	1.0	D	0.738	prob.delet.	N	0.507134781	None	None	N
Y/T	0.8054	likely_pathogenic	0.81	pathogenic	-2.861	Highly Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
Y/V	0.7194	likely_pathogenic	0.7267	pathogenic	-2.014	Highly Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
Y/W	0.4829	ambiguous	0.5369	ambiguous	-0.78	Destabilizing	1.0	D	0.715	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.