TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31525	94798;94799;94800	chr2:178546855;178546854;178546853	chr2:179411582;179411581;179411580
N2AB	29884	89875;89876;89877	chr2:178546855;178546854;178546853	chr2:179411582;179411581;179411580
N2A	28957	87094;87095;87096	chr2:178546855;178546854;178546853	chr2:179411582;179411581;179411580
N2B	22460	67603;67604;67605	chr2:178546855;178546854;178546853	chr2:179411582;179411581;179411580
Novex-1	22585	67978;67979;67980	chr2:178546855;178546854;178546853	chr2:179411582;179411581;179411580
Novex-2	22652	68179;68180;68181	chr2:178546855;178546854;178546853	chr2:179411582;179411581;179411580
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-118
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0781
• 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
L/M	rs1297210935	None	0.999	D	0.688	0.455	0.725964355292	gnomAD-2.1.1	4.12E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.13E-06	0
L/M	rs1297210935	None	0.999	D	0.688	0.455	0.725964355292	gnomAD-4.0.0	1.62134E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.93011E-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
L/A	0.9793	likely_pathogenic	0.9734	pathogenic	-2.509	Highly Destabilizing	0.994	D	0.671	neutral	None	None	None	None	N
L/C	0.9525	likely_pathogenic	0.9459	pathogenic	-1.233	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9999	pathogenic	-3.078	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/E	0.9991	likely_pathogenic	0.9989	pathogenic	-2.753	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
L/F	0.8747	likely_pathogenic	0.8597	pathogenic	-1.486	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
L/G	0.9978	likely_pathogenic	0.9974	pathogenic	-3.092	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/H	0.9981	likely_pathogenic	0.9979	pathogenic	-2.93	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
L/I	0.1701	likely_benign	0.1369	benign	-0.734	Destabilizing	0.833	D	0.319	neutral	None	None	None	None	N
L/K	0.9984	likely_pathogenic	0.9982	pathogenic	-1.732	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
L/M	0.3882	ambiguous	0.3492	ambiguous	-0.845	Destabilizing	0.999	D	0.688	prob.neutral	D	0.530446442	None	None	N
L/N	0.999	likely_pathogenic	0.9989	pathogenic	-2.514	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/P	0.9993	likely_pathogenic	0.9992	pathogenic	-1.32	Destabilizing	1.0	D	0.893	deleterious	D	0.569225846	None	None	N
L/Q	0.9965	likely_pathogenic	0.9959	pathogenic	-2.083	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.569225846	None	None	N
L/R	0.9965	likely_pathogenic	0.9961	pathogenic	-2.02	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.569225846	None	None	N
L/S	0.9982	likely_pathogenic	0.9977	pathogenic	-2.913	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/T	0.9873	likely_pathogenic	0.9833	pathogenic	-2.426	Highly Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
L/V	0.2014	likely_benign	0.1694	benign	-1.32	Destabilizing	0.962	D	0.597	neutral	N	0.48155391	None	None	N
L/W	0.9962	likely_pathogenic	0.9957	pathogenic	-1.802	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
L/Y	0.9952	likely_pathogenic	0.9947	pathogenic	-1.657	Destabilizing	1.0	D	0.768	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.