TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24193	72802;72803;72804	chr2:178573555;178573554;178573553	chr2:179438282;179438281;179438280
N2AB	22552	67879;67880;67881	chr2:178573555;178573554;178573553	chr2:179438282;179438281;179438280
N2A	21625	65098;65099;65100	chr2:178573555;178573554;178573553	chr2:179438282;179438281;179438280
N2B	15128	45607;45608;45609	chr2:178573555;178573554;178573553	chr2:179438282;179438281;179438280
Novex-1	15253	45982;45983;45984	chr2:178573555;178573554;178573553	chr2:179438282;179438281;179438280
Novex-2	15320	46183;46184;46185	chr2:178573555;178573554;178573553	chr2:179438282;179438281;179438280
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: Fn3-63
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.0999
• 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	0.885	0.861	0.896531243126	gnomAD-4.0.0	1.95251E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.37437E-06	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	0.9974	likely_pathogenic	0.9972	pathogenic	-3.289	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
Y/C	0.9788	likely_pathogenic	0.9803	pathogenic	-1.925	Destabilizing	1.0	D	0.885	deleterious	D	0.696848854	None	None	N
Y/D	0.9933	likely_pathogenic	0.9929	pathogenic	-3.253	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.696848854	None	None	N
Y/E	0.9986	likely_pathogenic	0.9986	pathogenic	-3.075	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/F	0.6734	likely_pathogenic	0.7131	pathogenic	-1.244	Destabilizing	0.999	D	0.755	deleterious	D	0.643956392	None	None	N
Y/G	0.9862	likely_pathogenic	0.9855	pathogenic	-3.691	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
Y/H	0.9931	likely_pathogenic	0.995	pathogenic	-2.086	Highly Destabilizing	1.0	D	0.839	deleterious	D	0.671310742	None	None	N
Y/I	0.9797	likely_pathogenic	0.9794	pathogenic	-1.961	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/K	0.999	likely_pathogenic	0.9991	pathogenic	-2.268	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/L	0.96	likely_pathogenic	0.9594	pathogenic	-1.961	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
Y/M	0.9873	likely_pathogenic	0.9866	pathogenic	-1.648	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
Y/N	0.9659	likely_pathogenic	0.9721	pathogenic	-2.924	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.696647049	None	None	N
Y/P	0.9991	likely_pathogenic	0.9991	pathogenic	-2.416	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/Q	0.9991	likely_pathogenic	0.9992	pathogenic	-2.75	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/R	0.9977	likely_pathogenic	0.998	pathogenic	-1.849	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/S	0.9905	likely_pathogenic	0.9912	pathogenic	-3.339	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.696848854	None	None	N
Y/T	0.9959	likely_pathogenic	0.9958	pathogenic	-3.05	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/V	0.9605	likely_pathogenic	0.9555	pathogenic	-2.416	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
Y/W	0.9616	likely_pathogenic	0.9705	pathogenic	-0.569	Destabilizing	1.0	D	0.826	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.