TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6398	19417;19418;19419	chr2:178728734;178728733;178728732	chr2:179593461;179593460;179593459
N2AB	6081	18466;18467;18468	chr2:178728734;178728733;178728732	chr2:179593461;179593460;179593459
N2A	5154	15685;15686;15687	chr2:178728734;178728733;178728732	chr2:179593461;179593460;179593459
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-48
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.4477
• 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	rs756732703	-0.552	0.051	N	0.133	0.121	0.203808441222	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
E/A	rs756732703	-0.552	0.051	N	0.133	0.121	0.203808441222	gnomAD-4.0.0	4.81468E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.30911E-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	0.1949	likely_benign	0.1959	benign	-0.681	Destabilizing	0.051	N	0.133	neutral	N	0.401472699	None	None	N
E/C	0.951	likely_pathogenic	0.9371	pathogenic	-0.285	Destabilizing	0.998	D	0.334	neutral	None	None	None	None	N
E/D	0.3742	ambiguous	0.365	ambiguous	-0.816	Destabilizing	0.012	N	0.167	neutral	N	0.453731103	None	None	N
E/F	0.9023	likely_pathogenic	0.9073	pathogenic	-0.343	Destabilizing	0.974	D	0.349	neutral	None	None	None	None	N
E/G	0.2587	likely_benign	0.2485	benign	-0.984	Destabilizing	0.669	D	0.368	neutral	N	0.482246748	None	None	N
E/H	0.7916	likely_pathogenic	0.7771	pathogenic	-0.515	Destabilizing	0.991	D	0.292	neutral	None	None	None	None	N
E/I	0.5349	ambiguous	0.5364	ambiguous	0.124	Stabilizing	0.728	D	0.392	neutral	None	None	None	None	N
E/K	0.2504	likely_benign	0.2265	benign	-0.306	Destabilizing	0.801	D	0.374	neutral	N	0.464177383	None	None	N
E/L	0.5801	likely_pathogenic	0.6021	pathogenic	0.124	Stabilizing	0.728	D	0.394	neutral	None	None	None	None	N
E/M	0.6211	likely_pathogenic	0.6351	pathogenic	0.437	Stabilizing	0.974	D	0.325	neutral	None	None	None	None	N
E/N	0.5829	likely_pathogenic	0.5711	pathogenic	-0.669	Destabilizing	0.728	D	0.349	neutral	None	None	None	None	N
E/P	0.8034	likely_pathogenic	0.7343	pathogenic	-0.123	Destabilizing	0.974	D	0.315	neutral	None	None	None	None	N
E/Q	0.2145	likely_benign	0.2056	benign	-0.583	Destabilizing	0.891	D	0.383	neutral	N	0.45715541	None	None	N
E/R	0.4287	ambiguous	0.4018	ambiguous	-0.068	Destabilizing	0.974	D	0.328	neutral	None	None	None	None	N
E/S	0.3409	ambiguous	0.3533	ambiguous	-0.914	Destabilizing	0.728	D	0.348	neutral	None	None	None	None	N
E/T	0.4691	ambiguous	0.4501	ambiguous	-0.671	Destabilizing	0.842	D	0.371	neutral	None	None	None	None	N
E/V	0.3112	likely_benign	0.3171	benign	-0.123	Destabilizing	0.022	N	0.14	neutral	N	0.428331226	None	None	N
E/W	0.961	likely_pathogenic	0.9618	pathogenic	-0.142	Destabilizing	0.998	D	0.501	neutral	None	None	None	None	N
E/Y	0.8509	likely_pathogenic	0.8563	pathogenic	-0.106	Destabilizing	0.991	D	0.33	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.