TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5632	17119;17120;17121	chr2:178732075;178732074;178732073	chr2:179596802;179596801;179596800
N2AB	5315	16168;16169;16170	chr2:178732075;178732074;178732073	chr2:179596802;179596801;179596800
N2A	4388	13387;13388;13389	chr2:178732075;178732074;178732073	chr2:179596802;179596801;179596800
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-39
• Domain position: 90
• Structural Position: 175
• Q(SASA): 0.5827
• 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
I/R	None	None	0.863	N	0.493	0.374	0.812764335004	gnomAD-4.0.0	6.88696E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0453E-07	0	0
I/T	rs727504971	None	0.003	N	0.179	0.258	0.659973416392	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs727504971	None	0.003	N	0.179	0.258	0.659973416392	gnomAD-4.0.0	1.87008E-06	None	None	None	None	N	None	2.67709E-05	0	None	0	0	None	0	0	8.52101E-07	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
I/A	0.1729	likely_benign	0.1392	benign	-1.417	Destabilizing	0.176	N	0.338	neutral	None	None	None	None	N
I/C	0.6306	likely_pathogenic	0.5889	pathogenic	-0.952	Destabilizing	0.981	D	0.422	neutral	None	None	None	None	N
I/D	0.495	ambiguous	0.4329	ambiguous	-0.336	Destabilizing	0.704	D	0.5	neutral	None	None	None	None	N
I/E	0.36	ambiguous	0.3017	benign	-0.304	Destabilizing	0.704	D	0.505	neutral	None	None	None	None	N
I/F	0.1194	likely_benign	0.111	benign	-0.832	Destabilizing	0.944	D	0.381	neutral	None	None	None	None	N
I/G	0.524	ambiguous	0.4696	ambiguous	-1.757	Destabilizing	0.704	D	0.49	neutral	None	None	None	None	N
I/H	0.3181	likely_benign	0.2734	benign	-0.927	Destabilizing	0.981	D	0.465	neutral	None	None	None	None	N
I/K	0.217	likely_benign	0.1892	benign	-0.823	Destabilizing	0.642	D	0.498	neutral	N	0.468101202	None	None	N
I/L	0.1042	likely_benign	0.1035	benign	-0.559	Destabilizing	0.139	N	0.262	neutral	N	0.48678575	None	None	N
I/M	0.0779	likely_benign	0.0743	benign	-0.531	Destabilizing	0.975	D	0.397	neutral	D	0.531923394	None	None	N
I/N	0.1883	likely_benign	0.1613	benign	-0.697	Destabilizing	0.704	D	0.489	neutral	None	None	None	None	N
I/P	0.753	likely_pathogenic	0.7474	pathogenic	-0.813	Destabilizing	0.944	D	0.495	neutral	None	None	None	None	N
I/Q	0.2778	likely_benign	0.2388	benign	-0.791	Destabilizing	0.944	D	0.501	neutral	None	None	None	None	N
I/R	0.1524	likely_benign	0.1357	benign	-0.375	Destabilizing	0.863	D	0.493	neutral	N	0.486612391	None	None	N
I/S	0.1749	likely_benign	0.1452	benign	-1.427	Destabilizing	0.037	N	0.189	neutral	None	None	None	None	N
I/T	0.0797	likely_benign	0.0684	benign	-1.27	Destabilizing	0.003	N	0.179	neutral	N	0.401838924	None	None	N
I/V	0.0746	likely_benign	0.0701	benign	-0.813	Destabilizing	0.139	N	0.267	neutral	N	0.471971013	None	None	N
I/W	0.5886	likely_pathogenic	0.571	pathogenic	-0.894	Destabilizing	0.995	D	0.504	neutral	None	None	None	None	N
I/Y	0.3669	ambiguous	0.3484	ambiguous	-0.651	Destabilizing	0.981	D	0.439	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.