TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3273	10042;10043;10044	chr2:178764698;178764697;178764696	chr2:179629425;179629424;179629423
N2AB	3273	10042;10043;10044	chr2:178764698;178764697;178764696	chr2:179629425;179629424;179629423
N2A	3273	10042;10043;10044	chr2:178764698;178764697;178764696	chr2:179629425;179629424;179629423
N2B	3227	9904;9905;9906	chr2:178764698;178764697;178764696	chr2:179629425;179629424;179629423
Novex-1	3227	9904;9905;9906	chr2:178764698;178764697;178764696	chr2:179629425;179629424;179629423
Novex-2	3227	9904;9905;9906	chr2:178764698;178764697;178764696	chr2:179629425;179629424;179629423
Novex-3	3273	10042;10043;10044	chr2:178764698;178764697;178764696	chr2:179629425;179629424;179629423

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-23
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.2109
• 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/N	rs2090039389	None	0.996	D	0.786	0.722	0.795880955708	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Y/N	rs2090039389	None	0.996	D	0.786	0.722	0.795880955708	gnomAD-4.0.0	6.57091E-06	None	None	None	None	N	None	2.4122E-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	0.9079	likely_pathogenic	0.9731	pathogenic	-2.7	Highly Destabilizing	0.944	D	0.673	neutral	None	None	None	None	N
Y/C	0.4327	ambiguous	0.7016	pathogenic	-1.238	Destabilizing	0.999	D	0.773	deleterious	D	0.697812385	None	None	N
Y/D	0.9054	likely_pathogenic	0.9759	pathogenic	-1.522	Destabilizing	0.996	D	0.793	deleterious	D	0.659822846	None	None	N
Y/E	0.9244	likely_pathogenic	0.979	pathogenic	-1.415	Destabilizing	0.997	D	0.764	deleterious	None	None	None	None	N
Y/F	0.0986	likely_benign	0.1122	benign	-1.139	Destabilizing	0.039	N	0.345	neutral	N	0.464187366	None	None	N
Y/G	0.8533	likely_pathogenic	0.9467	pathogenic	-3.029	Highly Destabilizing	0.992	D	0.754	deleterious	None	None	None	None	N
Y/H	0.3202	likely_benign	0.5557	ambiguous	-1.309	Destabilizing	0.996	D	0.73	prob.delet.	D	0.555169237	None	None	N
Y/I	0.8287	likely_pathogenic	0.9365	pathogenic	-1.675	Destabilizing	0.968	D	0.715	prob.delet.	None	None	None	None	N
Y/K	0.8095	likely_pathogenic	0.9314	pathogenic	-1.298	Destabilizing	0.992	D	0.765	deleterious	None	None	None	None	N
Y/L	0.712	likely_pathogenic	0.8444	pathogenic	-1.675	Destabilizing	0.895	D	0.522	neutral	None	None	None	None	N
Y/M	0.8211	likely_pathogenic	0.9108	pathogenic	-1.338	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
Y/N	0.5888	likely_pathogenic	0.8146	pathogenic	-1.584	Destabilizing	0.996	D	0.786	deleterious	D	0.586926347	None	None	N
Y/P	0.9981	likely_pathogenic	0.9995	pathogenic	-2.017	Highly Destabilizing	0.997	D	0.791	deleterious	None	None	None	None	N
Y/Q	0.7801	likely_pathogenic	0.9291	pathogenic	-1.574	Destabilizing	0.997	D	0.799	deleterious	None	None	None	None	N
Y/R	0.6402	likely_pathogenic	0.8428	pathogenic	-0.777	Destabilizing	0.992	D	0.786	deleterious	None	None	None	None	N
Y/S	0.6631	likely_pathogenic	0.8731	pathogenic	-2.178	Highly Destabilizing	0.989	D	0.753	deleterious	N	0.515236562	None	None	N
Y/T	0.8547	likely_pathogenic	0.9522	pathogenic	-1.977	Destabilizing	0.992	D	0.757	deleterious	None	None	None	None	N
Y/V	0.7659	likely_pathogenic	0.9039	pathogenic	-2.017	Highly Destabilizing	0.895	D	0.659	neutral	None	None	None	None	N
Y/W	0.5423	ambiguous	0.6075	pathogenic	-0.543	Destabilizing	0.999	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.