TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31042	93349;93350;93351	chr2:178548502;178548501;178548500	chr2:179413229;179413228;179413227
N2AB	29401	88426;88427;88428	chr2:178548502;178548501;178548500	chr2:179413229;179413228;179413227
N2A	28474	85645;85646;85647	chr2:178548502;178548501;178548500	chr2:179413229;179413228;179413227
N2B	21977	66154;66155;66156	chr2:178548502;178548501;178548500	chr2:179413229;179413228;179413227
Novex-1	22102	66529;66530;66531	chr2:178548502;178548501;178548500	chr2:179413229;179413228;179413227
Novex-2	22169	66730;66731;66732	chr2:178548502;178548501;178548500	chr2:179413229;179413228;179413227
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: Fn3-114
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.6494
• 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
L/P	rs1575474263	None	0.995	N	0.595	0.422	0.754779769779	gnomAD-4.0.0	1.36835E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79888E-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	0.2342	likely_benign	0.2215	benign	-0.496	Destabilizing	0.919	D	0.444	neutral	None	None	None	None	I
L/C	0.4688	ambiguous	0.4578	ambiguous	-0.632	Destabilizing	0.999	D	0.497	neutral	None	None	None	None	I
L/D	0.5641	likely_pathogenic	0.5234	ambiguous	-0.031	Destabilizing	0.851	D	0.54	neutral	None	None	None	None	I
L/E	0.335	likely_benign	0.3249	benign	-0.121	Destabilizing	0.919	D	0.528	neutral	None	None	None	None	I
L/F	0.1455	likely_benign	0.1291	benign	-0.542	Destabilizing	0.995	D	0.405	neutral	N	0.437014998	None	None	I
L/G	0.5027	ambiguous	0.4658	ambiguous	-0.646	Destabilizing	0.851	D	0.519	neutral	None	None	None	None	I
L/H	0.1582	likely_benign	0.1463	benign	0.009	Stabilizing	0.984	D	0.577	neutral	N	0.426414003	None	None	I
L/I	0.0948	likely_benign	0.0981	benign	-0.225	Destabilizing	0.982	D	0.42	neutral	N	0.361325161	None	None	I
L/K	0.3189	likely_benign	0.3063	benign	-0.257	Destabilizing	0.919	D	0.524	neutral	None	None	None	None	I
L/M	0.1182	likely_benign	0.1146	benign	-0.383	Destabilizing	0.996	D	0.423	neutral	None	None	None	None	I
L/N	0.2126	likely_benign	0.2004	benign	-0.067	Destabilizing	0.015	N	0.282	neutral	None	None	None	None	I
L/P	0.6352	likely_pathogenic	0.605	pathogenic	-0.283	Destabilizing	0.995	D	0.595	neutral	N	0.450656299	None	None	I
L/Q	0.1305	likely_benign	0.124	benign	-0.263	Destabilizing	0.988	D	0.575	neutral	None	None	None	None	I
L/R	0.2197	likely_benign	0.2124	benign	0.234	Stabilizing	0.968	D	0.5	neutral	N	0.431627821	None	None	I
L/S	0.2283	likely_benign	0.206	benign	-0.515	Destabilizing	0.851	D	0.512	neutral	None	None	None	None	I
L/T	0.1922	likely_benign	0.1784	benign	-0.494	Destabilizing	0.919	D	0.463	neutral	None	None	None	None	I
L/V	0.1027	likely_benign	0.1068	benign	-0.283	Destabilizing	0.946	D	0.456	neutral	N	0.404518578	None	None	I
L/W	0.2319	likely_benign	0.2033	benign	-0.567	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	I
L/Y	0.2842	likely_benign	0.2563	benign	-0.31	Destabilizing	0.996	D	0.458	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.