TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14733	44422;44423;44424	chr2:178630325;178630324;178630323	chr2:179495052;179495051;179495050
N2AB	13092	39499;39500;39501	chr2:178630325;178630324;178630323	chr2:179495052;179495051;179495050
N2A	12165	36718;36719;36720	chr2:178630325;178630324;178630323	chr2:179495052;179495051;179495050
N2B	5668	17227;17228;17229	chr2:178630325;178630324;178630323	chr2:179495052;179495051;179495050
Novex-1	5793	17602;17603;17604	chr2:178630325;178630324;178630323	chr2:179495052;179495051;179495050
Novex-2	5860	17803;17804;17805	chr2:178630325;178630324;178630323	chr2:179495052;179495051;179495050
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-98
• Domain position: 59
• Structural Position: 140
• Q(SASA): 0.1997
• 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/S	None	None	0.999	D	0.879	0.526	0.730100223331	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.9647	likely_pathogenic	0.9742	pathogenic	-3.012	Highly Destabilizing	0.998	D	0.744	deleterious	None	None	None	None	N
L/C	0.9324	likely_pathogenic	0.9463	pathogenic	-2.472	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
L/D	0.9984	likely_pathogenic	0.9989	pathogenic	-3.358	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/E	0.9889	likely_pathogenic	0.9924	pathogenic	-3.142	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
L/F	0.3558	ambiguous	0.3971	ambiguous	-1.89	Destabilizing	0.999	D	0.83	deleterious	N	0.511111677	None	None	N
L/G	0.9926	likely_pathogenic	0.9948	pathogenic	-3.577	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
L/H	0.9416	likely_pathogenic	0.9595	pathogenic	-2.916	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/I	0.1299	likely_benign	0.1427	benign	-1.37	Destabilizing	0.998	D	0.543	neutral	None	None	None	None	N
L/K	0.968	likely_pathogenic	0.9794	pathogenic	-2.525	Highly Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
L/M	0.2836	likely_benign	0.328	benign	-1.271	Destabilizing	0.999	D	0.815	deleterious	D	0.542361737	None	None	N
L/N	0.9893	likely_pathogenic	0.9934	pathogenic	-2.835	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/P	0.994	likely_pathogenic	0.9955	pathogenic	-1.899	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
L/Q	0.9307	likely_pathogenic	0.951	pathogenic	-2.729	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
L/R	0.9368	likely_pathogenic	0.9522	pathogenic	-2.093	Highly Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
L/S	0.9841	likely_pathogenic	0.9886	pathogenic	-3.568	Highly Destabilizing	0.999	D	0.879	deleterious	D	0.605397585	None	None	N
L/T	0.9599	likely_pathogenic	0.9722	pathogenic	-3.199	Highly Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
L/V	0.2873	likely_benign	0.3069	benign	-1.899	Destabilizing	0.997	D	0.521	neutral	N	0.506346501	None	None	N
L/W	0.7799	likely_pathogenic	0.8176	pathogenic	-2.248	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.606217409	None	None	N
L/Y	0.8703	likely_pathogenic	0.9	pathogenic	-2.051	Highly Destabilizing	0.999	D	0.863	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.