TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32420	97483;97484;97485	chr2:178542498;178542497;178542496	chr2:179407225;179407224;179407223
N2AB	30779	92560;92561;92562	chr2:178542498;178542497;178542496	chr2:179407225;179407224;179407223
N2A	29852	89779;89780;89781	chr2:178542498;178542497;178542496	chr2:179407225;179407224;179407223
N2B	23355	70288;70289;70290	chr2:178542498;178542497;178542496	chr2:179407225;179407224;179407223
Novex-1	23480	70663;70664;70665	chr2:178542498;178542497;178542496	chr2:179407225;179407224;179407223
Novex-2	23547	70864;70865;70866	chr2:178542498;178542497;178542496	chr2:179407225;179407224;179407223
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-124
• Domain position: 22
• Structural Position: 23
• Q(SASA): 0.2529
• 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
S/F	rs1393812138	None	1.0	D	0.895	0.442	0.793893798558	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.1223	likely_benign	0.0872	benign	-0.79	Destabilizing	0.997	D	0.461	neutral	N	0.48675815	None	None	N
S/C	0.1508	likely_benign	0.1119	benign	-0.604	Destabilizing	1.0	D	0.829	deleterious	N	0.505902817	None	None	N
S/D	0.7452	likely_pathogenic	0.6521	pathogenic	-1.241	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
S/E	0.7269	likely_pathogenic	0.6302	pathogenic	-1.098	Destabilizing	0.999	D	0.553	neutral	None	None	None	None	N
S/F	0.3386	likely_benign	0.2434	benign	-0.69	Destabilizing	1.0	D	0.895	deleterious	D	0.535109887	None	None	N
S/G	0.1516	likely_benign	0.1145	benign	-1.149	Destabilizing	0.999	D	0.542	neutral	None	None	None	None	N
S/H	0.4318	ambiguous	0.3521	ambiguous	-1.558	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
S/I	0.3526	ambiguous	0.2546	benign	0.101	Stabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
S/K	0.7652	likely_pathogenic	0.6664	pathogenic	-0.43	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
S/L	0.1969	likely_benign	0.1395	benign	0.101	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
S/M	0.2931	likely_benign	0.227	benign	0.098	Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
S/N	0.3383	likely_benign	0.2588	benign	-0.938	Destabilizing	0.999	D	0.554	neutral	None	None	None	None	N
S/P	0.979	likely_pathogenic	0.9649	pathogenic	-0.161	Destabilizing	1.0	D	0.823	deleterious	D	0.546630777	None	None	N
S/Q	0.5799	likely_pathogenic	0.491	ambiguous	-0.814	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
S/R	0.6611	likely_pathogenic	0.5513	ambiguous	-0.665	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
S/T	0.101	likely_benign	0.0881	benign	-0.673	Destabilizing	0.999	D	0.503	neutral	N	0.516078789	None	None	N
S/V	0.3524	ambiguous	0.242	benign	-0.161	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
S/W	0.5163	ambiguous	0.4333	ambiguous	-0.893	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
S/Y	0.3527	ambiguous	0.2579	benign	-0.48	Destabilizing	1.0	D	0.9	deleterious	D	0.528526522	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.