TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28681	86266;86267;86268	chr2:178560091;178560090;178560089	chr2:179424818;179424817;179424816
N2AB	27040	81343;81344;81345	chr2:178560091;178560090;178560089	chr2:179424818;179424817;179424816
N2A	26113	78562;78563;78564	chr2:178560091;178560090;178560089	chr2:179424818;179424817;179424816
N2B	19616	59071;59072;59073	chr2:178560091;178560090;178560089	chr2:179424818;179424817;179424816
Novex-1	19741	59446;59447;59448	chr2:178560091;178560090;178560089	chr2:179424818;179424817;179424816
Novex-2	19808	59647;59648;59649	chr2:178560091;178560090;178560089	chr2:179424818;179424817;179424816
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-97
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2016
• Predicted PPI site: I

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
A/V	None	None	0.201	N	0.67	0.253	0.445210270852	gnomAD-4.0.0	1.36848E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.73491E-04	8.99462E-07	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
A/C	0.3187	likely_benign	0.3288	benign	-0.778	Destabilizing	0.947	D	0.722	prob.delet.	None	None	None	None	I
A/D	0.5248	ambiguous	0.552	ambiguous	-0.863	Destabilizing	0.638	D	0.706	prob.neutral	N	0.487177247	None	None	I
A/E	0.4499	ambiguous	0.4613	ambiguous	-0.994	Destabilizing	0.7	D	0.707	prob.neutral	None	None	None	None	I
A/F	0.3484	ambiguous	0.3341	benign	-1.063	Destabilizing	0.826	D	0.713	prob.delet.	None	None	None	None	I
A/G	0.1665	likely_benign	0.1633	benign	-0.723	Destabilizing	0.201	N	0.614	neutral	N	0.480707061	None	None	I
A/H	0.5498	ambiguous	0.5557	ambiguous	-0.82	Destabilizing	0.947	D	0.714	prob.delet.	None	None	None	None	I
A/I	0.3688	ambiguous	0.3614	ambiguous	-0.452	Destabilizing	0.539	D	0.706	prob.neutral	None	None	None	None	I
A/K	0.7369	likely_pathogenic	0.7439	pathogenic	-0.968	Destabilizing	0.539	D	0.707	prob.neutral	None	None	None	None	I
A/L	0.1965	likely_benign	0.1924	benign	-0.452	Destabilizing	0.25	N	0.669	neutral	None	None	None	None	I
A/M	0.2125	likely_benign	0.2131	benign	-0.329	Destabilizing	0.947	D	0.689	prob.neutral	None	None	None	None	I
A/N	0.377	ambiguous	0.3862	ambiguous	-0.571	Destabilizing	0.539	D	0.709	prob.delet.	None	None	None	None	I
A/P	0.9698	likely_pathogenic	0.9695	pathogenic	-0.463	Destabilizing	0.781	D	0.707	prob.neutral	N	0.495526654	None	None	I
A/Q	0.4693	ambiguous	0.4594	ambiguous	-0.867	Destabilizing	0.7	D	0.694	prob.neutral	None	None	None	None	I
A/R	0.6906	likely_pathogenic	0.6951	pathogenic	-0.47	Destabilizing	0.7	D	0.703	prob.neutral	None	None	None	None	I
A/S	0.0727	likely_benign	0.0716	benign	-0.804	Destabilizing	0.007	N	0.435	neutral	N	0.39745932	None	None	I
A/T	0.1093	likely_benign	0.1073	benign	-0.857	Destabilizing	0.002	N	0.517	neutral	N	0.493353858	None	None	I
A/V	0.1884	likely_benign	0.1778	benign	-0.463	Destabilizing	0.201	N	0.67	neutral	N	0.518326873	None	None	I
A/W	0.8319	likely_pathogenic	0.8286	pathogenic	-1.24	Destabilizing	0.982	D	0.743	deleterious	None	None	None	None	I
A/Y	0.5041	ambiguous	0.4919	ambiguous	-0.895	Destabilizing	0.826	D	0.717	prob.delet.	None	None	None	None	I

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.