TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32697	98314;98315;98316	chr2:178540077;178540076;178540075	chr2:179404804;179404803;179404802
N2AB	31056	93391;93392;93393	chr2:178540077;178540076;178540075	chr2:179404804;179404803;179404802
N2A	30129	90610;90611;90612	chr2:178540077;178540076;178540075	chr2:179404804;179404803;179404802
N2B	23632	71119;71120;71121	chr2:178540077;178540076;178540075	chr2:179404804;179404803;179404802
Novex-1	23757	71494;71495;71496	chr2:178540077;178540076;178540075	chr2:179404804;179404803;179404802
Novex-2	23824	71695;71696;71697	chr2:178540077;178540076;178540075	chr2:179404804;179404803;179404802
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-126
• Domain position: 98
• Structural Position: 132
• Q(SASA): 0.7108
• 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
E/D	rs748057839	-0.025	0.997	N	0.586	0.142	0.274366138417	gnomAD-2.1.1	2.95E-05	None	None	None	None	N	None	0	0	None	0	4.11862E-04	None	0	None	0	0	0
E/D	rs748057839	-0.025	0.997	N	0.586	0.142	0.274366138417	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92976E-04	None	0	0	0	0	0
E/D	rs748057839	-0.025	0.997	N	0.586	0.142	0.274366138417	gnomAD-4.0.0	6.25188E-06	None	None	None	None	N	None	0	0	None	0	2.01279E-04	None	0	0	0	0	1.61943E-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
E/A	0.7932	likely_pathogenic	0.7735	pathogenic	-0.102	Destabilizing	0.997	D	0.735	deleterious	N	0.508814461	None	None	N
E/C	0.9951	likely_pathogenic	0.9948	pathogenic	0.112	Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
E/D	0.317	likely_benign	0.2948	benign	-0.183	Destabilizing	0.997	D	0.586	neutral	N	0.445168414	None	None	N
E/F	0.9968	likely_pathogenic	0.9965	pathogenic	-0.154	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/G	0.8163	likely_pathogenic	0.7995	pathogenic	-0.237	Destabilizing	0.999	D	0.601	neutral	N	0.492276149	None	None	N
E/H	0.9788	likely_pathogenic	0.9756	pathogenic	0.201	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/I	0.9852	likely_pathogenic	0.9832	pathogenic	0.199	Stabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
E/K	0.877	likely_pathogenic	0.8626	pathogenic	0.585	Stabilizing	0.997	D	0.715	prob.delet.	N	0.482993304	None	None	N
E/L	0.9763	likely_pathogenic	0.9747	pathogenic	0.199	Stabilizing	0.999	D	0.701	prob.delet.	None	None	None	None	N
E/M	0.9792	likely_pathogenic	0.9764	pathogenic	0.196	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/N	0.8759	likely_pathogenic	0.847	pathogenic	0.355	Stabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
E/P	0.9291	likely_pathogenic	0.9101	pathogenic	0.118	Stabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
E/Q	0.7561	likely_pathogenic	0.7377	pathogenic	0.369	Stabilizing	0.999	D	0.649	prob.neutral	N	0.501097559	None	None	N
E/R	0.938	likely_pathogenic	0.9296	pathogenic	0.685	Stabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
E/S	0.8392	likely_pathogenic	0.8125	pathogenic	0.219	Stabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
E/T	0.934	likely_pathogenic	0.9225	pathogenic	0.335	Stabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
E/V	0.9395	likely_pathogenic	0.9345	pathogenic	0.118	Stabilizing	0.999	D	0.711	prob.delet.	N	0.503885944	None	None	N
E/W	0.9985	likely_pathogenic	0.9982	pathogenic	-0.091	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/Y	0.991	likely_pathogenic	0.9897	pathogenic	0.077	Stabilizing	1.0	D	0.763	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.