TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6662	20209;20210;20211	chr2:178727594;178727593;178727592	chr2:179592321;179592320;179592319
N2AB	6345	19258;19259;19260	chr2:178727594;178727593;178727592	chr2:179592321;179592320;179592319
N2A	5418	16477;16478;16479	chr2:178727594;178727593;178727592	chr2:179592321;179592320;179592319
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: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-50
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.2379
• 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/F	rs2079581150	None	0.006	N	0.14	0.13	0.38342384377	gnomAD-4.0.0	1.72006E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.64447E-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
L/A	0.1552	likely_benign	0.1375	benign	-1.222	Destabilizing	0.495	N	0.435	neutral	None	None	None	None	N
L/C	0.5087	ambiguous	0.4448	ambiguous	-0.691	Destabilizing	0.995	D	0.427	neutral	None	None	None	None	N
L/D	0.4184	ambiguous	0.3734	ambiguous	-0.606	Destabilizing	0.543	D	0.565	neutral	None	None	None	None	N
L/E	0.1912	likely_benign	0.1935	benign	-0.663	Destabilizing	0.031	N	0.45	neutral	None	None	None	None	N
L/F	0.0957	likely_benign	0.089	benign	-0.985	Destabilizing	0.006	N	0.14	neutral	N	0.385045462	None	None	N
L/G	0.4327	ambiguous	0.379	ambiguous	-1.474	Destabilizing	0.543	D	0.557	neutral	None	None	None	None	N
L/H	0.1323	likely_benign	0.1223	benign	-0.693	Destabilizing	0.927	D	0.515	neutral	N	0.472144371	None	None	N
L/I	0.0787	likely_benign	0.0728	benign	-0.64	Destabilizing	0.006	N	0.253	neutral	N	0.403649865	None	None	N
L/K	0.2046	likely_benign	0.2013	benign	-0.704	Destabilizing	0.704	D	0.522	neutral	None	None	None	None	N
L/M	0.0927	likely_benign	0.0908	benign	-0.444	Destabilizing	0.176	N	0.295	neutral	None	None	None	None	N
L/N	0.2423	likely_benign	0.2048	benign	-0.428	Destabilizing	0.017	N	0.457	neutral	None	None	None	None	N
L/P	0.6377	likely_pathogenic	0.6192	pathogenic	-0.801	Destabilizing	0.975	D	0.553	neutral	N	0.520706322	None	None	N
L/Q	0.0989	likely_benign	0.1011	benign	-0.68	Destabilizing	0.893	D	0.523	neutral	None	None	None	None	N
L/R	0.1363	likely_benign	0.1406	benign	-0.082	Destabilizing	0.863	D	0.525	neutral	N	0.455193406	None	None	N
L/S	0.1571	likely_benign	0.1328	benign	-0.987	Destabilizing	0.543	D	0.518	neutral	None	None	None	None	N
L/T	0.116	likely_benign	0.1059	benign	-0.935	Destabilizing	0.013	N	0.159	neutral	None	None	None	None	N
L/V	0.0767	likely_benign	0.0732	benign	-0.801	Destabilizing	0.27	N	0.337	neutral	N	0.420888832	None	None	N
L/W	0.1771	likely_benign	0.1732	benign	-0.994	Destabilizing	0.995	D	0.483	neutral	None	None	None	None	N
L/Y	0.2382	likely_benign	0.2241	benign	-0.766	Destabilizing	0.807	D	0.468	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.