TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24100	72523;72524;72525	chr2:178573834;178573833;178573832	chr2:179438561;179438560;179438559
N2AB	22459	67600;67601;67602	chr2:178573834;178573833;178573832	chr2:179438561;179438560;179438559
N2A	21532	64819;64820;64821	chr2:178573834;178573833;178573832	chr2:179438561;179438560;179438559
N2B	15035	45328;45329;45330	chr2:178573834;178573833;178573832	chr2:179438561;179438560;179438559
Novex-1	15160	45703;45704;45705	chr2:178573834;178573833;178573832	chr2:179438561;179438560;179438559
Novex-2	15227	45904;45905;45906	chr2:178573834;178573833;178573832	chr2:179438561;179438560;179438559
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-131
• Domain position: 72
• Structural Position: 154
• Q(SASA): 0.1302
• 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/S	None	None	0.051	D	0.651	0.638	0.80158762225	gnomAD-4.0.0	4.78495E-06	None	None	None	None	N	None	0	0	None	0	8.34168E-05	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	0.9956	likely_pathogenic	0.9957	pathogenic	-1.266	Destabilizing	0.525	D	0.777	deleterious	None	None	None	None	N
Y/C	0.8278	likely_pathogenic	0.8779	pathogenic	-0.968	Destabilizing	0.997	D	0.853	deleterious	D	0.659924006	None	None	N
Y/D	0.9982	likely_pathogenic	0.9972	pathogenic	-2.079	Highly Destabilizing	0.934	D	0.822	deleterious	D	0.659924006	None	None	N
Y/E	0.9992	likely_pathogenic	0.9989	pathogenic	-1.842	Destabilizing	0.949	D	0.802	deleterious	None	None	None	None	N
Y/F	0.0946	likely_benign	0.115	benign	-0.339	Destabilizing	0.005	N	0.362	neutral	D	0.557409029	None	None	N
Y/G	0.9951	likely_pathogenic	0.9945	pathogenic	-1.681	Destabilizing	0.728	D	0.811	deleterious	None	None	None	None	N
Y/H	0.9523	likely_pathogenic	0.9547	pathogenic	-1.74	Destabilizing	0.989	D	0.637	neutral	D	0.659722202	None	None	N
Y/I	0.911	likely_pathogenic	0.9158	pathogenic	0.09	Stabilizing	0.842	D	0.743	deleterious	None	None	None	None	N
Y/K	0.9987	likely_pathogenic	0.9982	pathogenic	-1.101	Destabilizing	0.949	D	0.804	deleterious	None	None	None	None	N
Y/L	0.8914	likely_pathogenic	0.9053	pathogenic	0.09	Stabilizing	0.525	D	0.715	prob.delet.	None	None	None	None	N
Y/M	0.9678	likely_pathogenic	0.9705	pathogenic	-0.238	Destabilizing	0.974	D	0.787	deleterious	None	None	None	None	N
Y/N	0.9889	likely_pathogenic	0.9857	pathogenic	-1.931	Destabilizing	0.934	D	0.807	deleterious	D	0.659924006	None	None	N
Y/P	0.9991	likely_pathogenic	0.9989	pathogenic	-0.374	Destabilizing	0.974	D	0.86	deleterious	None	None	None	None	N
Y/Q	0.9982	likely_pathogenic	0.9979	pathogenic	-1.411	Destabilizing	0.974	D	0.774	deleterious	None	None	None	None	N
Y/R	0.9948	likely_pathogenic	0.9934	pathogenic	-1.737	Destabilizing	0.949	D	0.847	deleterious	None	None	None	None	N
Y/S	0.9901	likely_pathogenic	0.9889	pathogenic	-2.153	Highly Destabilizing	0.051	N	0.651	neutral	D	0.659924006	None	None	N
Y/T	0.9948	likely_pathogenic	0.9947	pathogenic	-1.768	Destabilizing	0.728	D	0.795	deleterious	None	None	None	None	N
Y/V	0.8722	likely_pathogenic	0.8841	pathogenic	-0.374	Destabilizing	0.842	D	0.728	prob.delet.	None	None	None	None	N
Y/W	0.6155	likely_pathogenic	0.6355	pathogenic	0.104	Stabilizing	0.991	D	0.667	neutral	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.