TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23271	70036;70037;70038	chr2:178576321;178576320;178576319	chr2:179441048;179441047;179441046
N2AB	21630	65113;65114;65115	chr2:178576321;178576320;178576319	chr2:179441048;179441047;179441046
N2A	20703	62332;62333;62334	chr2:178576321;178576320;178576319	chr2:179441048;179441047;179441046
N2B	14206	42841;42842;42843	chr2:178576321;178576320;178576319	chr2:179441048;179441047;179441046
Novex-1	14331	43216;43217;43218	chr2:178576321;178576320;178576319	chr2:179441048;179441047;179441046
Novex-2	14398	43417;43418;43419	chr2:178576321;178576320;178576319	chr2:179441048;179441047;179441046
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-57
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.8484
• 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
E/G	rs779955364	-0.363	0.822	N	0.627	0.241	0.343101102393	gnomAD-2.1.1	4.82E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.03E-05	0
E/G	rs779955364	-0.363	0.822	N	0.627	0.241	0.343101102393	gnomAD-4.0.0	1.40882E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.82615E-06	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
E/A	0.129	likely_benign	0.1169	benign	-0.272	Destabilizing	0.698	D	0.635	neutral	N	0.447890927	None	None	I
E/C	0.7874	likely_pathogenic	0.7523	pathogenic	-0.033	Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	I
E/D	0.0901	likely_benign	0.0886	benign	-0.278	Destabilizing	0.006	N	0.101	neutral	N	0.440367522	None	None	I
E/F	0.7712	likely_pathogenic	0.7274	pathogenic	-0.185	Destabilizing	0.993	D	0.667	neutral	None	None	None	None	I
E/G	0.1887	likely_benign	0.1647	benign	-0.46	Destabilizing	0.822	D	0.627	neutral	N	0.450643231	None	None	I
E/H	0.4486	ambiguous	0.4113	ambiguous	0.102	Stabilizing	0.978	D	0.558	neutral	None	None	None	None	I
E/I	0.3855	ambiguous	0.3448	ambiguous	0.182	Stabilizing	0.978	D	0.676	prob.neutral	None	None	None	None	I
E/K	0.1899	likely_benign	0.171	benign	0.343	Stabilizing	0.014	N	0.231	neutral	N	0.398078182	None	None	I
E/L	0.374	ambiguous	0.3357	benign	0.182	Stabilizing	0.956	D	0.62	neutral	None	None	None	None	I
E/M	0.4575	ambiguous	0.4207	ambiguous	0.203	Stabilizing	0.998	D	0.662	neutral	None	None	None	None	I
E/N	0.2096	likely_benign	0.1925	benign	0.078	Stabilizing	0.16	N	0.23	neutral	None	None	None	None	I
E/P	0.2214	likely_benign	0.1836	benign	0.051	Stabilizing	0.978	D	0.641	neutral	None	None	None	None	I
E/Q	0.1458	likely_benign	0.1349	benign	0.109	Stabilizing	0.822	D	0.556	neutral	N	0.489545548	None	None	I
E/R	0.2901	likely_benign	0.2634	benign	0.559	Stabilizing	0.915	D	0.542	neutral	None	None	None	None	I
E/S	0.1882	likely_benign	0.1749	benign	-0.095	Destabilizing	0.86	D	0.556	neutral	None	None	None	None	I
E/T	0.2186	likely_benign	0.2044	benign	0.057	Stabilizing	0.86	D	0.625	neutral	None	None	None	None	I
E/V	0.2177	likely_benign	0.1919	benign	0.051	Stabilizing	0.942	D	0.617	neutral	N	0.492951213	None	None	I
E/W	0.904	likely_pathogenic	0.8741	pathogenic	-0.061	Destabilizing	0.998	D	0.746	deleterious	None	None	None	None	I
E/Y	0.6303	likely_pathogenic	0.5754	pathogenic	0.055	Stabilizing	0.993	D	0.671	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.