TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20709	62350;62351;62352	chr2:178589600;178589599;178589598	chr2:179454327;179454326;179454325
N2AB	19068	57427;57428;57429	chr2:178589600;178589599;178589598	chr2:179454327;179454326;179454325
N2A	18141	54646;54647;54648	chr2:178589600;178589599;178589598	chr2:179454327;179454326;179454325
N2B	11644	35155;35156;35157	chr2:178589600;178589599;178589598	chr2:179454327;179454326;179454325
Novex-1	11769	35530;35531;35532	chr2:178589600;178589599;178589598	chr2:179454327;179454326;179454325
Novex-2	11836	35731;35732;35733	chr2:178589600;178589599;178589598	chr2:179454327;179454326;179454325
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: Fn3-38
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2712
• 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	rs371705537	-1.113	0.996	N	0.391	0.161	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
L/F	rs371705537	-1.113	0.996	N	0.391	0.161	None	gnomAD-3.1.2	3.95E-05	None	None	None	None	N	None	1.4483E-04	0	0	0	0	None	0	0	0	0	0
L/F	rs371705537	-1.113	0.996	N	0.391	0.161	None	gnomAD-4.0.0	5.57906E-06	None	None	None	None	N	None	1.06869E-04	0	None	0	0	None	0	0	0	0	1.60138E-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
L/A	0.2131	likely_benign	0.2548	benign	-1.635	Destabilizing	0.079	N	0.123	neutral	None	None	None	None	N
L/C	0.5415	ambiguous	0.6347	pathogenic	-0.923	Destabilizing	0.999	D	0.391	neutral	None	None	None	None	N
L/D	0.72	likely_pathogenic	0.8091	pathogenic	-0.805	Destabilizing	0.046	N	0.309	neutral	None	None	None	None	N
L/E	0.3283	likely_benign	0.3851	ambiguous	-0.768	Destabilizing	0.884	D	0.409	neutral	None	None	None	None	N
L/F	0.2063	likely_benign	0.2801	benign	-1.031	Destabilizing	0.996	D	0.391	neutral	N	0.488350683	None	None	N
L/G	0.4781	ambiguous	0.5729	pathogenic	-1.989	Destabilizing	0.884	D	0.429	neutral	None	None	None	None	N
L/H	0.2849	likely_benign	0.3738	ambiguous	-1.107	Destabilizing	0.999	D	0.457	neutral	N	0.458470493	None	None	N
L/I	0.1102	likely_benign	0.1303	benign	-0.725	Destabilizing	0.92	D	0.309	neutral	N	0.435921707	None	None	N
L/K	0.1717	likely_benign	0.1973	benign	-1.016	Destabilizing	0.939	D	0.413	neutral	None	None	None	None	N
L/M	0.1135	likely_benign	0.1503	benign	-0.598	Destabilizing	0.997	D	0.42	neutral	None	None	None	None	N
L/N	0.3785	ambiguous	0.4589	ambiguous	-0.868	Destabilizing	0.982	D	0.461	neutral	None	None	None	None	N
L/P	0.153	likely_benign	0.2053	benign	-0.998	Destabilizing	0.988	D	0.465	neutral	N	0.395707094	None	None	N
L/Q	0.1208	likely_benign	0.1444	benign	-0.984	Destabilizing	0.991	D	0.476	neutral	None	None	None	None	N
L/R	0.1836	likely_benign	0.232	benign	-0.482	Destabilizing	0.988	D	0.454	neutral	N	0.408292389	None	None	N
L/S	0.2901	likely_benign	0.3818	ambiguous	-1.548	Destabilizing	0.884	D	0.394	neutral	None	None	None	None	N
L/T	0.2331	likely_benign	0.2851	benign	-1.385	Destabilizing	0.17	N	0.157	neutral	None	None	None	None	N
L/V	0.105	likely_benign	0.1323	benign	-0.998	Destabilizing	0.826	D	0.361	neutral	N	0.458297135	None	None	N
L/W	0.3738	ambiguous	0.51	ambiguous	-1.107	Destabilizing	0.999	D	0.497	neutral	None	None	None	None	N
L/Y	0.4172	ambiguous	0.5369	ambiguous	-0.879	Destabilizing	0.997	D	0.413	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.