TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7208	21847;21848;21849	chr2:178723478;178723477;178723476	chr2:179588205;179588204;179588203
N2AB	6891	20896;20897;20898	chr2:178723478;178723477;178723476	chr2:179588205;179588204;179588203
N2A	5964	18115;18116;18117	chr2:178723478;178723477;178723476	chr2:179588205;179588204;179588203
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-56
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1698
• 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
T/I	rs1250736680	-0.273	0.961	N	0.647	0.357	0.467839254973	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	0	0	0
T/I	rs1250736680	-0.273	0.961	N	0.647	0.357	0.467839254973	gnomAD-4.0.0	2.05326E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69886E-06	0	0
T/N	rs1250736680	None	0.994	N	0.615	0.37	0.44318313171	gnomAD-4.0.0	2.73769E-06	None	None	None	None	N	None	0	6.71652E-05	None	0	0	None	0	0	0	0	1.6575E-05

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
T/A	0.1101	likely_benign	0.1197	benign	-1.125	Destabilizing	0.911	D	0.607	neutral	N	0.493741184	None	None	N
T/C	0.563	ambiguous	0.5853	pathogenic	-0.615	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
T/D	0.6217	likely_pathogenic	0.6421	pathogenic	-1.199	Destabilizing	0.996	D	0.677	prob.neutral	None	None	None	None	N
T/E	0.4786	ambiguous	0.4896	ambiguous	-1.003	Destabilizing	0.985	D	0.647	neutral	None	None	None	None	N
T/F	0.3475	ambiguous	0.3749	ambiguous	-0.859	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
T/G	0.3944	ambiguous	0.4264	ambiguous	-1.533	Destabilizing	0.985	D	0.651	neutral	None	None	None	None	N
T/H	0.2923	likely_benign	0.3154	benign	-1.641	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
T/I	0.2429	likely_benign	0.2457	benign	-0.054	Destabilizing	0.961	D	0.647	neutral	N	0.471838267	None	None	N
T/K	0.2664	likely_benign	0.2815	benign	-0.198	Destabilizing	0.971	D	0.637	neutral	None	None	None	None	N
T/L	0.1601	likely_benign	0.1667	benign	-0.054	Destabilizing	0.971	D	0.649	neutral	None	None	None	None	N
T/M	0.1248	likely_benign	0.1316	benign	-0.036	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
T/N	0.2069	likely_benign	0.2214	benign	-0.846	Destabilizing	0.994	D	0.615	neutral	N	0.489982202	None	None	N
T/P	0.6933	likely_pathogenic	0.7416	pathogenic	-0.381	Destabilizing	0.997	D	0.709	prob.delet.	D	0.524469192	None	None	N
T/Q	0.287	likely_benign	0.3011	benign	-0.651	Destabilizing	0.996	D	0.713	prob.delet.	None	None	None	None	N
T/R	0.1691	likely_benign	0.1882	benign	-0.456	Destabilizing	0.323	N	0.517	neutral	None	None	None	None	N
T/S	0.1171	likely_benign	0.1312	benign	-1.111	Destabilizing	0.659	D	0.529	neutral	N	0.469140486	None	None	N
T/V	0.2046	likely_benign	0.2062	benign	-0.381	Destabilizing	0.469	N	0.522	neutral	None	None	None	None	N
T/W	0.7276	likely_pathogenic	0.7617	pathogenic	-0.978	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
T/Y	0.3768	ambiguous	0.4029	ambiguous	-0.59	Destabilizing	0.999	D	0.744	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.