TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6344	19255;19256;19257	chr2:178729008;178729007;178729006	chr2:179593735;179593734;179593733
N2AB	6027	18304;18305;18306	chr2:178729008;178729007;178729006	chr2:179593735;179593734;179593733
N2A	5100	15523;15524;15525	chr2:178729008;178729007;178729006	chr2:179593735;179593734;179593733
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-47
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.9015
• Predicted PPI site: I

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/E	rs750787195	-0.151	0.012	N	0.19	0.057	0.0762999501168	gnomAD-4.0.0	8.21481E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.07964E-05	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	0.1969	likely_benign	0.1958	benign	-0.004	Destabilizing	0.024	N	0.262	neutral	N	0.457199825	None	None	I
D/C	0.5583	ambiguous	0.5801	pathogenic	-0.274	Destabilizing	0.864	D	0.234	neutral	None	None	None	None	I
D/E	0.1856	likely_benign	0.181	benign	-0.43	Destabilizing	0.012	N	0.19	neutral	N	0.439238866	None	None	I
D/F	0.6667	likely_pathogenic	0.6663	pathogenic	-0.02	Destabilizing	0.628	D	0.27	neutral	None	None	None	None	I
D/G	0.1035	likely_benign	0.1045	benign	-0.116	Destabilizing	0.005	N	0.224	neutral	N	0.457320408	None	None	I
D/H	0.1799	likely_benign	0.1997	benign	0.642	Stabilizing	0.171	N	0.269	neutral	N	0.463556154	None	None	I
D/I	0.6274	likely_pathogenic	0.6231	pathogenic	0.226	Stabilizing	0.356	N	0.313	neutral	None	None	None	None	I
D/K	0.2912	likely_benign	0.3135	benign	0.42	Stabilizing	0.016	N	0.27	neutral	None	None	None	None	I
D/L	0.4993	ambiguous	0.4981	ambiguous	0.226	Stabilizing	0.072	N	0.314	neutral	None	None	None	None	I
D/M	0.7003	likely_pathogenic	0.698	pathogenic	-0.032	Destabilizing	0.628	D	0.235	neutral	None	None	None	None	I
D/N	0.0613	likely_benign	0.0633	benign	0.008	Stabilizing	None	N	0.091	neutral	N	0.413727133	None	None	I
D/P	0.6197	likely_pathogenic	0.6398	pathogenic	0.168	Stabilizing	0.136	N	0.309	neutral	None	None	None	None	I
D/Q	0.2721	likely_benign	0.2817	benign	0.03	Stabilizing	0.072	N	0.199	neutral	None	None	None	None	I
D/R	0.3068	likely_benign	0.3265	benign	0.68	Stabilizing	0.072	N	0.311	neutral	None	None	None	None	I
D/S	0.1031	likely_benign	0.1069	benign	-0.026	Destabilizing	0.007	N	0.157	neutral	None	None	None	None	I
D/T	0.3184	likely_benign	0.3168	benign	0.076	Stabilizing	0.016	N	0.303	neutral	None	None	None	None	I
D/V	0.4571	ambiguous	0.4499	ambiguous	0.168	Stabilizing	0.106	N	0.339	neutral	N	0.472456924	None	None	I
D/W	0.841	likely_pathogenic	0.8468	pathogenic	0.036	Stabilizing	0.864	D	0.343	neutral	None	None	None	None	I
D/Y	0.2387	likely_benign	0.2536	benign	0.203	Stabilizing	0.56	D	0.277	neutral	N	0.472456924	None	None	I

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.