TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24530	73813;73814;73815	chr2:178572544;178572543;178572542	chr2:179437271;179437270;179437269
N2AB	22889	68890;68891;68892	chr2:178572544;178572543;178572542	chr2:179437271;179437270;179437269
N2A	21962	66109;66110;66111	chr2:178572544;178572543;178572542	chr2:179437271;179437270;179437269
N2B	15465	46618;46619;46620	chr2:178572544;178572543;178572542	chr2:179437271;179437270;179437269
Novex-1	15590	46993;46994;46995	chr2:178572544;178572543;178572542	chr2:179437271;179437270;179437269
Novex-2	15657	47194;47195;47196	chr2:178572544;178572543;178572542	chr2:179437271;179437270;179437269
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-66
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.1278
• 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
E/A	None	None	0.859	N	0.554	0.293	0.424549175451	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
E/D	None	None	0.14	N	0.403	0.033	0.112648838833	gnomAD-4.0.0	6.84351E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99593E-07	0	0
E/K	None	None	0.919	N	0.477	0.267	0.369867359543	gnomAD-4.0.0	1.36869E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99585E-07	1.15955E-05	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
E/A	0.2646	likely_benign	0.2341	benign	-0.507	Destabilizing	0.859	D	0.554	neutral	N	0.479611218	None	None	N
E/C	0.8977	likely_pathogenic	0.9005	pathogenic	-0.151	Destabilizing	0.998	D	0.673	neutral	None	None	None	None	N
E/D	0.0863	likely_benign	0.0929	benign	-0.517	Destabilizing	0.14	N	0.403	neutral	N	0.452525956	None	None	N
E/F	0.8577	likely_pathogenic	0.8483	pathogenic	-0.243	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	N
E/G	0.3278	likely_benign	0.2761	benign	-0.755	Destabilizing	0.91	D	0.517	neutral	N	0.485802963	None	None	N
E/H	0.694	likely_pathogenic	0.6747	pathogenic	-0.182	Destabilizing	0.987	D	0.588	neutral	None	None	None	None	N
E/I	0.6005	likely_pathogenic	0.6001	pathogenic	0.128	Stabilizing	0.98	D	0.677	prob.neutral	None	None	None	None	N
E/K	0.5428	ambiguous	0.4974	ambiguous	0.133	Stabilizing	0.919	D	0.477	neutral	N	0.485335664	None	None	N
E/L	0.6501	likely_pathogenic	0.6222	pathogenic	0.128	Stabilizing	0.98	D	0.657	neutral	None	None	None	None	N
E/M	0.6544	likely_pathogenic	0.6464	pathogenic	0.277	Stabilizing	0.99	D	0.595	neutral	None	None	None	None	N
E/N	0.31	likely_benign	0.2979	benign	-0.268	Destabilizing	0.023	N	0.26	neutral	None	None	None	None	N
E/P	0.9753	likely_pathogenic	0.9658	pathogenic	-0.063	Destabilizing	0.958	D	0.616	neutral	None	None	None	None	N
E/Q	0.3439	ambiguous	0.3083	benign	-0.207	Destabilizing	0.966	D	0.545	neutral	N	0.48039814	None	None	N
E/R	0.6985	likely_pathogenic	0.6563	pathogenic	0.353	Stabilizing	0.981	D	0.576	neutral	None	None	None	None	N
E/S	0.3248	likely_benign	0.2965	benign	-0.445	Destabilizing	0.802	D	0.488	neutral	None	None	None	None	N
E/T	0.364	ambiguous	0.35	ambiguous	-0.242	Destabilizing	0.975	D	0.57	neutral	None	None	None	None	N
E/V	0.4012	ambiguous	0.3854	ambiguous	-0.063	Destabilizing	0.964	D	0.623	neutral	N	0.49751489	None	None	N
E/W	0.9506	likely_pathogenic	0.9485	pathogenic	-0.043	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
E/Y	0.7317	likely_pathogenic	0.7165	pathogenic	0.009	Stabilizing	0.999	D	0.629	neutral	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.