TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18203	54832;54833;54834	chr2:178604080;178604079;178604078	chr2:179468807;179468806;179468805
N2AB	16562	49909;49910;49911	chr2:178604080;178604079;178604078	chr2:179468807;179468806;179468805
N2A	15635	47128;47129;47130	chr2:178604080;178604079;178604078	chr2:179468807;179468806;179468805
N2B	9138	27637;27638;27639	chr2:178604080;178604079;178604078	chr2:179468807;179468806;179468805
Novex-1	9263	28012;28013;28014	chr2:178604080;178604079;178604078	chr2:179468807;179468806;179468805
Novex-2	9330	28213;28214;28215	chr2:178604080;178604079;178604078	chr2:179468807;179468806;179468805
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: Fn3-20
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0797
• 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/P	rs771560830	-1.421	1.0	N	0.933	0.71	0.80784574723	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
L/P	rs771560830	-1.421	1.0	N	0.933	0.71	0.80784574723	gnomAD-4.0.0	4.78005E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.58846E-06	0	0
L/V	None	None	0.999	N	0.589	0.203	0.388495093706	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
L/A	0.9491	likely_pathogenic	0.9486	pathogenic	-2.769	Highly Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
L/C	0.9634	likely_pathogenic	0.959	pathogenic	-1.691	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9995	pathogenic	-3.296	Highly Destabilizing	1.0	D	0.937	deleterious	None	None	None	None	N
L/E	0.9962	likely_pathogenic	0.9951	pathogenic	-3.008	Highly Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
L/F	0.9177	likely_pathogenic	0.8952	pathogenic	-1.69	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/G	0.9934	likely_pathogenic	0.9931	pathogenic	-3.281	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
L/H	0.9973	likely_pathogenic	0.996	pathogenic	-2.921	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
L/I	0.1952	likely_benign	0.1736	benign	-1.194	Destabilizing	0.999	D	0.568	neutral	None	None	None	None	N
L/K	0.9954	likely_pathogenic	0.9942	pathogenic	-2.19	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
L/M	0.4583	ambiguous	0.4098	ambiguous	-1.355	Destabilizing	1.0	D	0.778	deleterious	N	0.480085879	None	None	N
L/N	0.9976	likely_pathogenic	0.9974	pathogenic	-2.941	Highly Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	N
L/P	0.9954	likely_pathogenic	0.9956	pathogenic	-1.717	Destabilizing	1.0	D	0.933	deleterious	N	0.508572162	None	None	N
L/Q	0.9922	likely_pathogenic	0.9893	pathogenic	-2.564	Highly Destabilizing	1.0	D	0.935	deleterious	N	0.519928467	None	None	N
L/R	0.9912	likely_pathogenic	0.9884	pathogenic	-2.338	Highly Destabilizing	1.0	D	0.918	deleterious	N	0.519928467	None	None	N
L/S	0.9973	likely_pathogenic	0.9968	pathogenic	-3.289	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
L/T	0.9705	likely_pathogenic	0.9623	pathogenic	-2.857	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/V	0.2499	likely_benign	0.2147	benign	-1.717	Destabilizing	0.999	D	0.589	neutral	N	0.424309486	None	None	N
L/W	0.9927	likely_pathogenic	0.9869	pathogenic	-1.87	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
L/Y	0.9936	likely_pathogenic	0.9909	pathogenic	-1.861	Destabilizing	1.0	D	0.891	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.