TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6215	18868;18869;18870	chr2:178729513;178729512;178729511	chr2:179594240;179594239;179594238
N2AB	5898	17917;17918;17919	chr2:178729513;178729512;178729511	chr2:179594240;179594239;179594238
N2A	4971	15136;15137;15138	chr2:178729513;178729512;178729511	chr2:179594240;179594239;179594238
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-46
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.3625
• 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
D/A	rs1267800654	-0.397	0.309	N	0.307	0.161	0.254761474806	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	8.9E-06	0
D/A	rs1267800654	-0.397	0.309	N	0.307	0.161	0.254761474806	gnomAD-4.0.0	3.18369E-06	None	None	None	None	N	None	5.66251E-05	0	None	0	0	None	0	0	2.85933E-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
D/A	0.1643	likely_benign	0.2033	benign	-0.509	Destabilizing	0.309	N	0.307	neutral	N	0.488224892	None	None	N
D/C	0.654	likely_pathogenic	0.7205	pathogenic	-0.114	Destabilizing	0.996	D	0.411	neutral	None	None	None	None	N
D/E	0.2113	likely_benign	0.2475	benign	-0.614	Destabilizing	0.007	N	0.105	neutral	N	0.457189909	None	None	N
D/F	0.6422	likely_pathogenic	0.713	pathogenic	-0.386	Destabilizing	0.984	D	0.401	neutral	None	None	None	None	N
D/G	0.1652	likely_benign	0.2102	benign	-0.798	Destabilizing	0.472	N	0.293	neutral	N	0.471518644	None	None	N
D/H	0.2709	likely_benign	0.3196	benign	-0.666	Destabilizing	0.939	D	0.355	neutral	N	0.457137372	None	None	N
D/I	0.4348	ambiguous	0.5147	ambiguous	0.233	Stabilizing	0.91	D	0.414	neutral	None	None	None	None	N
D/K	0.4257	ambiguous	0.4998	ambiguous	-0.312	Destabilizing	0.59	D	0.283	neutral	None	None	None	None	N
D/L	0.4481	ambiguous	0.5171	ambiguous	0.233	Stabilizing	0.742	D	0.359	neutral	None	None	None	None	N
D/M	0.6467	likely_pathogenic	0.7017	pathogenic	0.664	Stabilizing	0.996	D	0.395	neutral	None	None	None	None	N
D/N	0.0883	likely_benign	0.0942	benign	-0.604	Destabilizing	0.028	N	0.177	neutral	N	0.439508225	None	None	N
D/P	0.5417	ambiguous	0.6189	pathogenic	0.01	Stabilizing	0.953	D	0.344	neutral	None	None	None	None	N
D/Q	0.3908	ambiguous	0.4567	ambiguous	-0.511	Destabilizing	0.59	D	0.288	neutral	None	None	None	None	N
D/R	0.4372	ambiguous	0.511	ambiguous	-0.185	Destabilizing	0.91	D	0.357	neutral	None	None	None	None	N
D/S	0.1106	likely_benign	0.1329	benign	-0.796	Destabilizing	0.101	N	0.155	neutral	None	None	None	None	N
D/T	0.2156	likely_benign	0.2678	benign	-0.572	Destabilizing	0.037	N	0.292	neutral	None	None	None	None	N
D/V	0.2698	likely_benign	0.3228	benign	0.01	Stabilizing	0.684	D	0.357	neutral	N	0.502135552	None	None	N
D/W	0.8932	likely_pathogenic	0.9206	pathogenic	-0.273	Destabilizing	0.996	D	0.545	neutral	None	None	None	None	N
D/Y	0.2778	likely_benign	0.3328	benign	-0.182	Destabilizing	0.979	D	0.399	neutral	N	0.483635418	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.