TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15262	46009;46010;46011	chr2:178620826;178620825;178620824	chr2:179485553;179485552;179485551
N2AB	13621	41086;41087;41088	chr2:178620826;178620825;178620824	chr2:179485553;179485552;179485551
N2A	12694	38305;38306;38307	chr2:178620826;178620825;178620824	chr2:179485553;179485552;179485551
N2B	6197	18814;18815;18816	chr2:178620826;178620825;178620824	chr2:179485553;179485552;179485551
Novex-1	6322	19189;19190;19191	chr2:178620826;178620825;178620824	chr2:179485553;179485552;179485551
Novex-2	6389	19390;19391;19392	chr2:178620826;178620825;178620824	chr2:179485553;179485552;179485551
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-104
• Domain position: 55
• Structural Position: 136
• Q(SASA): 0.1412
• 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
Y/F	rs2058153201	None	0.031	N	0.351	0.196	0.206339911435	gnomAD-4.0.0	1.5934E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0303E-05
Y/S	None	None	0.998	N	0.804	0.521	0.459729313489	gnomAD-4.0.0	3.18679E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86673E-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
Y/A	0.9624	likely_pathogenic	0.9392	pathogenic	-2.921	Highly Destabilizing	0.985	D	0.776	deleterious	None	None	None	None	N
Y/C	0.4927	ambiguous	0.3476	ambiguous	-1.753	Destabilizing	1.0	D	0.781	deleterious	N	0.441867591	None	None	N
Y/D	0.9832	likely_pathogenic	0.9745	pathogenic	-2.641	Highly Destabilizing	0.998	D	0.839	deleterious	N	0.476253081	None	None	N
Y/E	0.9942	likely_pathogenic	0.9918	pathogenic	-2.468	Highly Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
Y/F	0.1476	likely_benign	0.1283	benign	-1.023	Destabilizing	0.031	N	0.351	neutral	N	0.421652289	None	None	N
Y/G	0.9659	likely_pathogenic	0.943	pathogenic	-3.325	Highly Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
Y/H	0.7034	likely_pathogenic	0.6718	pathogenic	-1.774	Destabilizing	0.998	D	0.763	deleterious	N	0.409677989	None	None	N
Y/I	0.9265	likely_pathogenic	0.8802	pathogenic	-1.607	Destabilizing	0.97	D	0.787	deleterious	None	None	None	None	N
Y/K	0.9899	likely_pathogenic	0.9862	pathogenic	-1.819	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
Y/L	0.8761	likely_pathogenic	0.813	pathogenic	-1.607	Destabilizing	0.871	D	0.753	deleterious	None	None	None	None	N
Y/M	0.9464	likely_pathogenic	0.9138	pathogenic	-1.41	Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	N
Y/N	0.8933	likely_pathogenic	0.8509	pathogenic	-2.411	Highly Destabilizing	0.998	D	0.813	deleterious	N	0.451022485	None	None	N
Y/P	0.9975	likely_pathogenic	0.9953	pathogenic	-2.054	Highly Destabilizing	0.999	D	0.84	deleterious	None	None	None	None	N
Y/Q	0.978	likely_pathogenic	0.9707	pathogenic	-2.242	Highly Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
Y/R	0.9687	likely_pathogenic	0.9613	pathogenic	-1.488	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
Y/S	0.8879	likely_pathogenic	0.8305	pathogenic	-2.905	Highly Destabilizing	0.998	D	0.804	deleterious	N	0.444883677	None	None	N
Y/T	0.96	likely_pathogenic	0.9387	pathogenic	-2.617	Highly Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
Y/V	0.8657	likely_pathogenic	0.7953	pathogenic	-2.054	Highly Destabilizing	0.97	D	0.767	deleterious	None	None	None	None	N
Y/W	0.6955	likely_pathogenic	0.6472	pathogenic	-0.364	Destabilizing	0.999	D	0.75	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.