TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29650	89173;89174;89175	chr2:178554163;178554162;178554161	chr2:179418890;179418889;179418888
N2AB	28009	84250;84251;84252	chr2:178554163;178554162;178554161	chr2:179418890;179418889;179418888
N2A	27082	81469;81470;81471	chr2:178554163;178554162;178554161	chr2:179418890;179418889;179418888
N2B	20585	61978;61979;61980	chr2:178554163;178554162;178554161	chr2:179418890;179418889;179418888
Novex-1	20710	62353;62354;62355	chr2:178554163;178554162;178554161	chr2:179418890;179418889;179418888
Novex-2	20777	62554;62555;62556	chr2:178554163;178554162;178554161	chr2:179418890;179418889;179418888
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-104
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0556
• 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
M/I	rs944381912	0.132	0.985	N	0.652	0.411	0.42130639912	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14811E-04	0	None	0	0	None	0	None	0	0	0
M/I	rs944381912	0.132	0.985	N	0.652	0.411	0.42130639912	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
M/I	rs944381912	0.132	0.985	N	0.652	0.411	0.42130639912	gnomAD-4.0.0	3.1047E-06	None	None	None	None	N	None	5.36021E-05	0	None	0	0	None	0	0	0	0	1.60452E-05
M/R	rs778289640	None	0.998	N	0.838	0.649	0.718718502515	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
M/R	rs778289640	None	0.998	N	0.838	0.649	0.718718502515	gnomAD-4.0.0	6.56961E-06	None	None	None	None	N	None	2.4115E-05	0	None	0	0	None	0	0	0	0	0
M/T	rs778289640	-1.437	0.994	N	0.807	0.557	0.824319612184	gnomAD-2.1.1	3.64E-05	None	None	None	None	N	None	0	0	None	0	4.13693E-04	None	3.41E-05	None	0	0	1.43225E-04
M/T	rs778289640	-1.437	0.994	N	0.807	0.557	0.824319612184	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	3.85505E-04	None	0	0	0	0	0
M/T	rs778289640	-1.437	0.994	N	0.807	0.557	0.824319612184	gnomAD-4.0.0	4.96719E-06	None	None	None	None	N	None	0	0	None	0	1.33749E-04	None	0	0	0	0	3.20873E-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
M/A	0.756	likely_pathogenic	0.7941	pathogenic	-1.959	Destabilizing	0.989	D	0.725	prob.delet.	None	None	None	None	N
M/C	0.8429	likely_pathogenic	0.8536	pathogenic	-2.531	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
M/D	0.9976	likely_pathogenic	0.9979	pathogenic	-2.19	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
M/E	0.9798	likely_pathogenic	0.9824	pathogenic	-1.94	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
M/F	0.8589	likely_pathogenic	0.8853	pathogenic	-0.592	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
M/G	0.9632	likely_pathogenic	0.9718	pathogenic	-2.429	Highly Destabilizing	0.995	D	0.79	deleterious	None	None	None	None	N
M/H	0.9822	likely_pathogenic	0.9859	pathogenic	-2.26	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
M/I	0.8544	likely_pathogenic	0.8777	pathogenic	-0.601	Destabilizing	0.985	D	0.652	neutral	N	0.427934155	None	None	N
M/K	0.9561	likely_pathogenic	0.9656	pathogenic	-1.261	Destabilizing	0.994	D	0.807	deleterious	N	0.514098208	None	None	N
M/L	0.5675	likely_pathogenic	0.5924	pathogenic	-0.601	Destabilizing	0.927	D	0.431	neutral	N	0.479800197	None	None	N
M/N	0.9799	likely_pathogenic	0.9823	pathogenic	-1.751	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
M/P	0.999	likely_pathogenic	0.9993	pathogenic	-1.038	Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	N
M/Q	0.8309	likely_pathogenic	0.8539	pathogenic	-1.379	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
M/R	0.9601	likely_pathogenic	0.9728	pathogenic	-1.557	Destabilizing	0.998	D	0.838	deleterious	N	0.514098208	None	None	N
M/S	0.883	likely_pathogenic	0.9069	pathogenic	-2.227	Highly Destabilizing	0.995	D	0.79	deleterious	None	None	None	None	N
M/T	0.8908	likely_pathogenic	0.9164	pathogenic	-1.845	Destabilizing	0.994	D	0.807	deleterious	N	0.487093183	None	None	N
M/V	0.3012	likely_benign	0.3452	ambiguous	-1.038	Destabilizing	0.985	D	0.523	neutral	N	0.435070771	None	None	N
M/W	0.9939	likely_pathogenic	0.9963	pathogenic	-0.967	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
M/Y	0.9863	likely_pathogenic	0.9893	pathogenic	-0.892	Destabilizing	0.999	D	0.844	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.