TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23194	69805;69806;69807	chr2:178576664;178576663;178576662	chr2:179441391;179441390;179441389
N2AB	21553	64882;64883;64884	chr2:178576664;178576663;178576662	chr2:179441391;179441390;179441389
N2A	20626	62101;62102;62103	chr2:178576664;178576663;178576662	chr2:179441391;179441390;179441389
N2B	14129	42610;42611;42612	chr2:178576664;178576663;178576662	chr2:179441391;179441390;179441389
Novex-1	14254	42985;42986;42987	chr2:178576664;178576663;178576662	chr2:179441391;179441390;179441389
Novex-2	14321	43186;43187;43188	chr2:178576664;178576663;178576662	chr2:179441391;179441390;179441389
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-56
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.1888
• 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
V/I	rs2046501912	None	0.003	N	0.227	0.08	0.165133752707	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs2046501912	None	0.003	N	0.227	0.08	0.165133752707	gnomAD-4.0.0	2.10732E-05	None	None	None	None	N	None	1.33561E-05	0	None	0	2.23025E-05	None	0	0	2.62798E-05	0	1.60149E-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
V/A	0.3651	ambiguous	0.4079	ambiguous	-1.744	Destabilizing	0.517	D	0.473	neutral	N	0.46492355	None	None	N
V/C	0.788	likely_pathogenic	0.79	pathogenic	-1.065	Destabilizing	0.996	D	0.676	prob.neutral	None	None	None	None	N
V/D	0.9197	likely_pathogenic	0.9362	pathogenic	-1.858	Destabilizing	0.983	D	0.752	deleterious	N	0.480861758	None	None	N
V/E	0.8294	likely_pathogenic	0.8643	pathogenic	-1.72	Destabilizing	0.987	D	0.687	prob.neutral	None	None	None	None	N
V/F	0.3737	ambiguous	0.3983	ambiguous	-1.088	Destabilizing	0.901	D	0.669	neutral	N	0.483903632	None	None	N
V/G	0.5168	ambiguous	0.5778	pathogenic	-2.21	Highly Destabilizing	0.949	D	0.714	prob.delet.	N	0.496066089	None	None	N
V/H	0.8792	likely_pathogenic	0.8985	pathogenic	-1.942	Destabilizing	0.996	D	0.745	deleterious	None	None	None	None	N
V/I	0.0848	likely_benign	0.0795	benign	-0.491	Destabilizing	0.003	N	0.227	neutral	N	0.439482087	None	None	N
V/K	0.8115	likely_pathogenic	0.8418	pathogenic	-1.358	Destabilizing	0.961	D	0.691	prob.neutral	None	None	None	None	N
V/L	0.2305	likely_benign	0.2409	benign	-0.491	Destabilizing	0.075	N	0.359	neutral	N	0.467850066	None	None	N
V/M	0.2393	likely_benign	0.2529	benign	-0.372	Destabilizing	0.923	D	0.605	neutral	None	None	None	None	N
V/N	0.7324	likely_pathogenic	0.7594	pathogenic	-1.386	Destabilizing	0.987	D	0.763	deleterious	None	None	None	None	N
V/P	0.9182	likely_pathogenic	0.9268	pathogenic	-0.877	Destabilizing	0.987	D	0.711	prob.delet.	None	None	None	None	N
V/Q	0.6883	likely_pathogenic	0.7443	pathogenic	-1.35	Destabilizing	0.987	D	0.722	prob.delet.	None	None	None	None	N
V/R	0.755	likely_pathogenic	0.7977	pathogenic	-1.109	Destabilizing	0.987	D	0.762	deleterious	None	None	None	None	N
V/S	0.5226	ambiguous	0.5796	pathogenic	-1.997	Destabilizing	0.961	D	0.645	neutral	None	None	None	None	N
V/T	0.3991	ambiguous	0.4399	ambiguous	-1.728	Destabilizing	0.775	D	0.55	neutral	None	None	None	None	N
V/W	0.9638	likely_pathogenic	0.9642	pathogenic	-1.52	Destabilizing	0.996	D	0.709	prob.delet.	None	None	None	None	N
V/Y	0.8382	likely_pathogenic	0.851	pathogenic	-1.137	Destabilizing	0.961	D	0.702	prob.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.