TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16090	48493;48494;48495	chr2:178616523;178616522;178616521	chr2:179481250;179481249;179481248
N2AB	14449	43570;43571;43572	chr2:178616523;178616522;178616521	chr2:179481250;179481249;179481248
N2A	13522	40789;40790;40791	chr2:178616523;178616522;178616521	chr2:179481250;179481249;179481248
N2B	7025	21298;21299;21300	chr2:178616523;178616522;178616521	chr2:179481250;179481249;179481248
Novex-1	7150	21673;21674;21675	chr2:178616523;178616522;178616521	chr2:179481250;179481249;179481248
Novex-2	7217	21874;21875;21876	chr2:178616523;178616522;178616521	chr2:179481250;179481249;179481248
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: Fn3-4
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1117
• 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	rs752903826	-2.001	1.0	D	0.883	0.776	0.884292940262	gnomAD-4.0.0	1.59404E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03141E-05

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	0.9956	pathogenic	-3.363	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/C	0.8761	likely_pathogenic	0.9188	pathogenic	-1.955	Destabilizing	1.0	D	0.883	deleterious	D	0.847016753	None	None	N
Y/D	0.9942	likely_pathogenic	0.9944	pathogenic	-3.776	Highly Destabilizing	1.0	D	0.923	deleterious	D	0.846003224	None	None	N
Y/E	0.9985	likely_pathogenic	0.9988	pathogenic	-3.546	Highly Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
Y/F	0.1397	likely_benign	0.1886	benign	-1.296	Destabilizing	0.999	D	0.635	neutral	D	0.648838997	None	None	N
Y/G	0.9857	likely_pathogenic	0.9877	pathogenic	-3.794	Highly Destabilizing	1.0	D	0.936	deleterious	None	None	None	None	N
Y/H	0.9661	likely_pathogenic	0.9772	pathogenic	-2.529	Highly Destabilizing	1.0	D	0.805	deleterious	D	0.814025288	None	None	N
Y/I	0.9563	likely_pathogenic	0.9667	pathogenic	-1.905	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/K	0.9978	likely_pathogenic	0.9985	pathogenic	-2.394	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
Y/L	0.9248	likely_pathogenic	0.9463	pathogenic	-1.905	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
Y/M	0.9682	likely_pathogenic	0.9785	pathogenic	-1.691	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
Y/N	0.9664	likely_pathogenic	0.9687	pathogenic	-3.247	Highly Destabilizing	1.0	D	0.908	deleterious	D	0.846003224	None	None	N
Y/P	0.9988	likely_pathogenic	0.9989	pathogenic	-2.411	Highly Destabilizing	1.0	D	0.951	deleterious	None	None	None	None	N
Y/Q	0.9976	likely_pathogenic	0.9984	pathogenic	-2.948	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
Y/R	0.9931	likely_pathogenic	0.9953	pathogenic	-2.247	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/S	0.9836	likely_pathogenic	0.9859	pathogenic	-3.571	Highly Destabilizing	1.0	D	0.917	deleterious	D	0.846003224	None	None	N
Y/T	0.9935	likely_pathogenic	0.9951	pathogenic	-3.213	Highly Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
Y/V	0.9424	likely_pathogenic	0.952	pathogenic	-2.411	Highly Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
Y/W	0.7619	likely_pathogenic	0.8072	pathogenic	-0.517	Destabilizing	1.0	D	0.793	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.