TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24552	73879;73880;73881	chr2:178572478;178572477;178572476	chr2:179437205;179437204;179437203
N2AB	22911	68956;68957;68958	chr2:178572478;178572477;178572476	chr2:179437205;179437204;179437203
N2A	21984	66175;66176;66177	chr2:178572478;178572477;178572476	chr2:179437205;179437204;179437203
N2B	15487	46684;46685;46686	chr2:178572478;178572477;178572476	chr2:179437205;179437204;179437203
Novex-1	15612	47059;47060;47061	chr2:178572478;178572477;178572476	chr2:179437205;179437204;179437203
Novex-2	15679	47260;47261;47262	chr2:178572478;178572477;178572476	chr2:179437205;179437204;179437203
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-66
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.263
• Predicted PPI site: I

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
K/Q	None	None	0.008	N	0.365	0.12	0.134241683229	gnomAD-4.0.0	1.59307E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43382E-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
K/A	0.6512	likely_pathogenic	0.4781	ambiguous	-0.304	Destabilizing	0.018	N	0.438	neutral	None	None	None	None	I
K/C	0.7448	likely_pathogenic	0.6078	pathogenic	-0.212	Destabilizing	0.879	D	0.349	neutral	None	None	None	None	I
K/D	0.8935	likely_pathogenic	0.7953	pathogenic	-0.261	Destabilizing	0.043	N	0.347	neutral	None	None	None	None	I
K/E	0.5233	ambiguous	0.3777	ambiguous	-0.194	Destabilizing	0.004	N	0.339	neutral	N	0.497354168	None	None	I
K/F	0.9203	likely_pathogenic	0.8496	pathogenic	-0.11	Destabilizing	0.201	N	0.385	neutral	None	None	None	None	I
K/G	0.7459	likely_pathogenic	0.542	ambiguous	-0.636	Destabilizing	0.018	N	0.364	neutral	None	None	None	None	I
K/H	0.4085	ambiguous	0.2774	benign	-1.084	Destabilizing	0.114	N	0.388	neutral	None	None	None	None	I
K/I	0.5118	ambiguous	0.4311	ambiguous	0.537	Stabilizing	0.009	N	0.403	neutral	None	None	None	None	I
K/L	0.5602	ambiguous	0.4123	ambiguous	0.537	Stabilizing	0.001	N	0.361	neutral	None	None	None	None	I
K/M	0.4489	ambiguous	0.319	benign	0.496	Stabilizing	0.148	N	0.385	neutral	N	0.52073246	None	None	I
K/N	0.659	likely_pathogenic	0.4369	ambiguous	-0.226	Destabilizing	None	N	0.119	neutral	N	0.475325457	None	None	I
K/P	0.9704	likely_pathogenic	0.9401	pathogenic	0.287	Stabilizing	0.387	N	0.404	neutral	None	None	None	None	I
K/Q	0.2395	likely_benign	0.162	benign	-0.358	Destabilizing	0.008	N	0.365	neutral	N	0.453526033	None	None	I
K/R	0.091	likely_benign	0.0797	benign	-0.56	Destabilizing	None	N	0.071	neutral	N	0.457470415	None	None	I
K/S	0.6632	likely_pathogenic	0.4558	ambiguous	-0.747	Destabilizing	0.001	N	0.125	neutral	None	None	None	None	I
K/T	0.2654	likely_benign	0.1794	benign	-0.499	Destabilizing	None	N	0.159	neutral	N	0.374889104	None	None	I
K/V	0.5122	ambiguous	0.417	ambiguous	0.287	Stabilizing	0.002	N	0.393	neutral	None	None	None	None	I
K/W	0.8735	likely_pathogenic	0.7819	pathogenic	-0.041	Destabilizing	0.915	D	0.465	neutral	None	None	None	None	I
K/Y	0.8229	likely_pathogenic	0.6961	pathogenic	0.245	Stabilizing	0.082	N	0.372	neutral	None	None	None	None	I

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.