TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13968	42127;42128;42129	chr2:178635287;178635286;178635285	chr2:179500014;179500013;179500012
N2AB	12327	37204;37205;37206	chr2:178635287;178635286;178635285	chr2:179500014;179500013;179500012
N2A	11400	34423;34424;34425	chr2:178635287;178635286;178635285	chr2:179500014;179500013;179500012
N2B	4903	14932;14933;14934	chr2:178635287;178635286;178635285	chr2:179500014;179500013;179500012
Novex-1	5028	15307;15308;15309	chr2:178635287;178635286;178635285	chr2:179500014;179500013;179500012
Novex-2	5095	15508;15509;15510	chr2:178635287;178635286;178635285	chr2:179500014;179500013;179500012
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-90
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4036
• 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
L/R	rs879228460	None	1.0	N	0.798	0.384	0.590611164678	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
L/R	rs879228460	None	1.0	N	0.798	0.384	0.590611164678	gnomAD-4.0.0	6.57393E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07211E-04	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
L/A	0.6311	likely_pathogenic	0.413	ambiguous	-0.959	Destabilizing	0.993	D	0.566	neutral	None	None	None	None	N
L/C	0.8424	likely_pathogenic	0.7673	pathogenic	-0.666	Destabilizing	1.0	D	0.689	prob.delet.	None	None	None	None	N
L/D	0.9494	likely_pathogenic	0.8811	pathogenic	-0.186	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
L/E	0.6815	likely_pathogenic	0.4912	ambiguous	-0.244	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
L/F	0.5913	likely_pathogenic	0.4028	ambiguous	-0.697	Destabilizing	0.999	D	0.69	prob.delet.	N	0.509278938	None	None	N
L/G	0.8789	likely_pathogenic	0.743	pathogenic	-1.184	Destabilizing	1.0	D	0.72	deleterious	None	None	None	None	N
L/H	0.6708	likely_pathogenic	0.4779	ambiguous	-0.325	Destabilizing	1.0	D	0.767	deleterious	N	0.510321716	None	None	N
L/I	0.1648	likely_benign	0.114	benign	-0.465	Destabilizing	0.983	D	0.473	neutral	N	0.432285559	None	None	N
L/K	0.4615	ambiguous	0.3101	benign	-0.535	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
L/M	0.2723	likely_benign	0.1897	benign	-0.433	Destabilizing	0.999	D	0.673	prob.neutral	None	None	None	None	N
L/N	0.7822	likely_pathogenic	0.5749	pathogenic	-0.34	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
L/P	0.9688	likely_pathogenic	0.9171	pathogenic	-0.596	Destabilizing	1.0	D	0.767	deleterious	N	0.5094858	None	None	N
L/Q	0.3817	ambiguous	0.2341	benign	-0.551	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
L/R	0.454	ambiguous	0.3152	benign	0.055	Stabilizing	1.0	D	0.798	deleterious	N	0.468529615	None	None	N
L/S	0.7578	likely_pathogenic	0.5041	ambiguous	-0.897	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
L/T	0.4863	ambiguous	0.2879	benign	-0.845	Destabilizing	0.998	D	0.708	prob.delet.	None	None	None	None	N
L/V	0.2041	likely_benign	0.1333	benign	-0.596	Destabilizing	0.603	D	0.307	neutral	N	0.437116006	None	None	N
L/W	0.8188	likely_pathogenic	0.6884	pathogenic	-0.699	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
L/Y	0.8142	likely_pathogenic	0.6659	pathogenic	-0.476	Destabilizing	1.0	D	0.725	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.