TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26565	79918;79919;79920	chr2:178566439;178566438;178566437	chr2:179431166;179431165;179431164
N2AB	24924	74995;74996;74997	chr2:178566439;178566438;178566437	chr2:179431166;179431165;179431164
N2A	23997	72214;72215;72216	chr2:178566439;178566438;178566437	chr2:179431166;179431165;179431164
N2B	17500	52723;52724;52725	chr2:178566439;178566438;178566437	chr2:179431166;179431165;179431164
Novex-1	17625	53098;53099;53100	chr2:178566439;178566438;178566437	chr2:179431166;179431165;179431164
Novex-2	17692	53299;53300;53301	chr2:178566439;178566438;178566437	chr2:179431166;179431165;179431164
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-81
• Domain position: 79
• Structural Position: 110
• Q(SASA): 0.0706
• 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
A/V	rs765196786	-0.926	1.0	D	0.716	0.718	0.70944288126	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	2.87687E-04	0	0
A/V	rs765196786	-0.926	1.0	D	0.716	0.718	0.70944288126	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.78927E-04

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
A/C	0.8363	likely_pathogenic	0.844	pathogenic	-1.882	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
A/D	0.9972	likely_pathogenic	0.9976	pathogenic	-3.115	Highly Destabilizing	1.0	D	0.793	deleterious	D	0.574740163	None	None	N
A/E	0.9961	likely_pathogenic	0.9967	pathogenic	-2.894	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
A/F	0.9871	likely_pathogenic	0.9887	pathogenic	-0.883	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
A/G	0.4044	ambiguous	0.4861	ambiguous	-2.215	Highly Destabilizing	1.0	D	0.64	neutral	D	0.546214201	None	None	N
A/H	0.9957	likely_pathogenic	0.9961	pathogenic	-2.251	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
A/I	0.9667	likely_pathogenic	0.9668	pathogenic	-0.511	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
A/K	0.9989	likely_pathogenic	0.9991	pathogenic	-1.637	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
A/L	0.9103	likely_pathogenic	0.9233	pathogenic	-0.511	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/M	0.962	likely_pathogenic	0.9661	pathogenic	-0.966	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
A/N	0.9889	likely_pathogenic	0.9895	pathogenic	-2.082	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
A/P	0.9297	likely_pathogenic	0.9422	pathogenic	-0.893	Destabilizing	1.0	D	0.829	deleterious	D	0.551355989	None	None	N
A/Q	0.988	likely_pathogenic	0.9903	pathogenic	-1.847	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
A/R	0.9942	likely_pathogenic	0.9951	pathogenic	-1.648	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
A/S	0.268	likely_benign	0.2705	benign	-2.452	Highly Destabilizing	1.0	D	0.634	neutral	N	0.514841083	None	None	N
A/T	0.7745	likely_pathogenic	0.7395	pathogenic	-2.12	Highly Destabilizing	1.0	D	0.795	deleterious	D	0.55536846	None	None	N
A/V	0.8565	likely_pathogenic	0.8491	pathogenic	-0.893	Destabilizing	1.0	D	0.716	prob.delet.	D	0.555114971	None	None	N
A/W	0.9988	likely_pathogenic	0.9991	pathogenic	-1.577	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
A/Y	0.9948	likely_pathogenic	0.9959	pathogenic	-1.214	Destabilizing	1.0	D	0.86	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.