TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8013	24262;24263;24264	chr2:178719353;178719352;178719351	chr2:179584080;179584079;179584078
N2AB	7696	23311;23312;23313	chr2:178719353;178719352;178719351	chr2:179584080;179584079;179584078
N2A	6769	20530;20531;20532	chr2:178719353;178719352;178719351	chr2:179584080;179584079;179584078
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: P
• RefSeq wild type transcript codon: CCG
• RefSeq wild type template codon: GGC
• Domain: Ig-65
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.8123
• 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
P/L	rs773761640	0.199	1.0	D	0.701	0.444	None	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	8.89E-06	0
P/L	rs773761640	0.199	1.0	D	0.701	0.444	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/L	rs773761640	0.199	1.0	D	0.701	0.444	None	gnomAD-4.0.0	5.57764E-06	None	None	None	None	I	None	2.67123E-05	1.66778E-05	None	0	0	None	0	0	4.23819E-06	1.09794E-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
P/A	0.2671	likely_benign	0.3899	ambiguous	-0.336	Destabilizing	1.0	D	0.652	neutral	N	0.484856636	None	None	I
P/C	0.8802	likely_pathogenic	0.9272	pathogenic	-0.708	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
P/D	0.7315	likely_pathogenic	0.7835	pathogenic	-0.15	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	I
P/E	0.61	likely_pathogenic	0.7104	pathogenic	-0.267	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
P/F	0.8597	likely_pathogenic	0.9173	pathogenic	-0.637	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
P/G	0.6813	likely_pathogenic	0.7321	pathogenic	-0.428	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
P/H	0.5625	ambiguous	0.6944	pathogenic	-0.044	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
P/I	0.743	likely_pathogenic	0.8368	pathogenic	-0.244	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
P/K	0.7002	likely_pathogenic	0.7962	pathogenic	-0.35	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
P/L	0.3794	ambiguous	0.5277	ambiguous	-0.244	Destabilizing	1.0	D	0.701	prob.neutral	D	0.533731548	None	None	I
P/M	0.682	likely_pathogenic	0.7933	pathogenic	-0.428	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	I
P/N	0.6587	likely_pathogenic	0.728	pathogenic	-0.137	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
P/Q	0.4778	ambiguous	0.6211	pathogenic	-0.347	Destabilizing	1.0	D	0.648	neutral	N	0.482512778	None	None	I
P/R	0.5189	ambiguous	0.6526	pathogenic	0.097	Stabilizing	1.0	D	0.687	prob.neutral	N	0.483566416	None	None	I
P/S	0.3826	ambiguous	0.5143	ambiguous	-0.479	Destabilizing	1.0	D	0.675	neutral	N	0.485439294	None	None	I
P/T	0.3434	ambiguous	0.4591	ambiguous	-0.495	Destabilizing	1.0	D	0.669	neutral	D	0.529285733	None	None	I
P/V	0.5622	ambiguous	0.6821	pathogenic	-0.243	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
P/W	0.9371	likely_pathogenic	0.9616	pathogenic	-0.713	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
P/Y	0.8324	likely_pathogenic	0.8891	pathogenic	-0.418	Destabilizing	1.0	D	0.662	neutral	None	None	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.