TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19357	58294;58295;58296	chr2:178594425;178594424;178594423	chr2:179459152;179459151;179459150
N2AB	17716	53371;53372;53373	chr2:178594425;178594424;178594423	chr2:179459152;179459151;179459150
N2A	16789	50590;50591;50592	chr2:178594425;178594424;178594423	chr2:179459152;179459151;179459150
N2B	10292	31099;31100;31101	chr2:178594425;178594424;178594423	chr2:179459152;179459151;179459150
Novex-1	10417	31474;31475;31476	chr2:178594425;178594424;178594423	chr2:179459152;179459151;179459150
Novex-2	10484	31675;31676;31677	chr2:178594425;178594424;178594423	chr2:179459152;179459151;179459150
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-28
• Domain position: 74
• Structural Position: 106
• Q(SASA): 0.0671
• 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	rs373907843	-1.517	0.995	N	0.881	0.382	None	gnomAD-2.1.1	1.62E-05	None	None	None	None	N	None	2.58565E-04	0	None	0	0	None	0	None	0	0	0
Y/C	rs373907843	-1.517	0.995	N	0.881	0.382	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.20662E-04	0	0	0	0	None	0	0	0	0	0
Y/C	rs373907843	-1.517	0.995	N	0.881	0.382	None	gnomAD-4.0.0	8.98118E-06	None	None	None	None	N	None	1.18495E-04	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	0.9944	likely_pathogenic	0.9943	pathogenic	-2.749	Highly Destabilizing	0.775	D	0.869	deleterious	None	None	None	None	N
Y/C	0.8541	likely_pathogenic	0.8684	pathogenic	-1.829	Destabilizing	0.995	D	0.881	deleterious	N	0.474989636	None	None	N
Y/D	0.9977	likely_pathogenic	0.9967	pathogenic	-3.545	Highly Destabilizing	0.983	D	0.903	deleterious	N	0.475496615	None	None	N
Y/E	0.9993	likely_pathogenic	0.9991	pathogenic	-3.313	Highly Destabilizing	0.987	D	0.901	deleterious	None	None	None	None	N
Y/F	0.0801	likely_benign	0.0758	benign	-1.086	Destabilizing	0.003	N	0.166	neutral	N	0.29975384	None	None	N
Y/G	0.9885	likely_pathogenic	0.9882	pathogenic	-3.184	Highly Destabilizing	0.961	D	0.911	deleterious	None	None	None	None	N
Y/H	0.9804	likely_pathogenic	0.9753	pathogenic	-2.193	Highly Destabilizing	0.983	D	0.747	deleterious	N	0.510958184	None	None	N
Y/I	0.8944	likely_pathogenic	0.9158	pathogenic	-1.299	Destabilizing	0.633	D	0.847	deleterious	None	None	None	None	N
Y/K	0.9992	likely_pathogenic	0.999	pathogenic	-2.539	Highly Destabilizing	0.961	D	0.901	deleterious	None	None	None	None	N
Y/L	0.8324	likely_pathogenic	0.8957	pathogenic	-1.299	Destabilizing	0.415	N	0.809	deleterious	None	None	None	None	N
Y/M	0.935	likely_pathogenic	0.9503	pathogenic	-1.082	Destabilizing	0.961	D	0.885	deleterious	None	None	None	None	N
Y/N	0.9872	likely_pathogenic	0.9849	pathogenic	-3.542	Highly Destabilizing	0.983	D	0.892	deleterious	N	0.475496615	None	None	N
Y/P	0.9993	likely_pathogenic	0.9993	pathogenic	-1.799	Destabilizing	0.987	D	0.923	deleterious	None	None	None	None	N
Y/Q	0.9989	likely_pathogenic	0.9987	pathogenic	-3.13	Highly Destabilizing	0.987	D	0.875	deleterious	None	None	None	None	N
Y/R	0.9982	likely_pathogenic	0.9979	pathogenic	-2.578	Highly Destabilizing	0.961	D	0.888	deleterious	None	None	None	None	N
Y/S	0.9928	likely_pathogenic	0.9915	pathogenic	-3.78	Highly Destabilizing	0.949	D	0.905	deleterious	N	0.521385821	None	None	N
Y/T	0.9952	likely_pathogenic	0.9949	pathogenic	-3.411	Highly Destabilizing	0.961	D	0.905	deleterious	None	None	None	None	N
Y/V	0.894	likely_pathogenic	0.9119	pathogenic	-1.799	Destabilizing	0.633	D	0.835	deleterious	None	None	None	None	N
Y/W	0.8479	likely_pathogenic	0.8145	pathogenic	-0.503	Destabilizing	0.987	D	0.785	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.