TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4801	14626;14627;14628	chr2:178736045;178736044;178736043	chr2:179600772;179600771;179600770
N2AB	4484	13675;13676;13677	chr2:178736045;178736044;178736043	chr2:179600772;179600771;179600770
N2A	3557	10894;10895;10896	chr2:178736045;178736044;178736043	chr2:179600772;179600771;179600770
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: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-31
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1861
• 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	rs780021536	-0.239	0.64	N	0.595	0.324	0.343101102393	gnomAD-2.1.1	4.22E-06	None	None	None	None	I	None	6.58E-05	0	None	0	0	None	0	None	0	0	0
P/L	rs780021536	-0.239	0.64	N	0.595	0.324	0.343101102393	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/L	rs780021536	-0.239	0.64	N	0.595	0.324	0.343101102393	gnomAD-4.0.0	6.57289E-06	None	None	None	None	I	None	2.41289E-05	0	None	0	0	None	0	0	0	0	0
P/T	None	None	0.999	N	0.781	0.4	0.312001716656	gnomAD-4.0.0	1.63352E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.90331E-05	0	0	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
P/A	0.5831	likely_pathogenic	0.6902	pathogenic	-1.68	Destabilizing	0.998	D	0.646	neutral	N	0.41937818	None	None	I
P/C	0.944	likely_pathogenic	0.9727	pathogenic	-1.049	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	I
P/D	0.9942	likely_pathogenic	0.9976	pathogenic	-1.572	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
P/E	0.9709	likely_pathogenic	0.9882	pathogenic	-1.44	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
P/F	0.9749	likely_pathogenic	0.9895	pathogenic	-0.99	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	I
P/G	0.9347	likely_pathogenic	0.9631	pathogenic	-2.144	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
P/H	0.9622	likely_pathogenic	0.9839	pathogenic	-1.798	Destabilizing	1.0	D	0.855	deleterious	N	0.4553486	None	None	I
P/I	0.7889	likely_pathogenic	0.8644	pathogenic	-0.439	Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	I
P/K	0.9798	likely_pathogenic	0.9929	pathogenic	-1.248	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
P/L	0.4526	ambiguous	0.5365	ambiguous	-0.439	Destabilizing	0.64	D	0.595	neutral	N	0.281982996	None	None	I
P/M	0.837	likely_pathogenic	0.8868	pathogenic	-0.371	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
P/N	0.9833	likely_pathogenic	0.9916	pathogenic	-1.247	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
P/Q	0.9189	likely_pathogenic	0.9624	pathogenic	-1.214	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
P/R	0.9557	likely_pathogenic	0.9831	pathogenic	-1.012	Destabilizing	1.0	D	0.863	deleterious	N	0.44940679	None	None	I
P/S	0.9105	likely_pathogenic	0.9525	pathogenic	-1.902	Destabilizing	1.0	D	0.781	deleterious	N	0.439620864	None	None	I
P/T	0.7915	likely_pathogenic	0.8708	pathogenic	-1.637	Destabilizing	0.999	D	0.781	deleterious	N	0.431825857	None	None	I
P/V	0.7149	likely_pathogenic	0.7968	pathogenic	-0.821	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	I
P/W	0.9928	likely_pathogenic	0.9979	pathogenic	-1.373	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
P/Y	0.9866	likely_pathogenic	0.9956	pathogenic	-1.003	Destabilizing	1.0	D	0.895	deleterious	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.