TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16535	49828;49829;49830	chr2:178613206;178613205;178613204	chr2:179477933;179477932;179477931
N2AB	14894	44905;44906;44907	chr2:178613206;178613205;178613204	chr2:179477933;179477932;179477931
N2A	13967	42124;42125;42126	chr2:178613206;178613205;178613204	chr2:179477933;179477932;179477931
N2B	7470	22633;22634;22635	chr2:178613206;178613205;178613204	chr2:179477933;179477932;179477931
Novex-1	7595	23008;23009;23010	chr2:178613206;178613205;178613204	chr2:179477933;179477932;179477931
Novex-2	7662	23209;23210;23211	chr2:178613206;178613205;178613204	chr2:179477933;179477932;179477931
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-7
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.6973
• 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/I	rs975321413	None	0.994	D	0.732	0.541	0.629195211289	gnomAD-4.0.0	1.37035E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80024E-06	0	0
K/Q	None	None	0.988	N	0.73	0.263	0.210429274316	gnomAD-4.0.0	2.0555E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.70035E-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
K/A	0.6985	likely_pathogenic	0.4585	ambiguous	-0.036	Destabilizing	0.968	D	0.677	prob.neutral	None	None	None	None	I
K/C	0.9067	likely_pathogenic	0.798	pathogenic	-0.208	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
K/D	0.8907	likely_pathogenic	0.7289	pathogenic	0.054	Stabilizing	0.982	D	0.691	prob.neutral	None	None	None	None	I
K/E	0.5513	ambiguous	0.33	benign	0.079	Stabilizing	0.958	D	0.631	neutral	N	0.416709197	None	None	I
K/F	0.9231	likely_pathogenic	0.8112	pathogenic	-0.128	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
K/G	0.8258	likely_pathogenic	0.6498	pathogenic	-0.271	Destabilizing	0.938	D	0.667	neutral	None	None	None	None	I
K/H	0.6184	likely_pathogenic	0.4588	ambiguous	-0.537	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	I
K/I	0.6046	likely_pathogenic	0.4075	ambiguous	0.512	Stabilizing	0.994	D	0.732	prob.delet.	D	0.54413394	None	None	I
K/L	0.569	likely_pathogenic	0.3859	ambiguous	0.512	Stabilizing	0.995	D	0.649	neutral	None	None	None	None	I
K/M	0.5075	ambiguous	0.3313	benign	0.251	Stabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
K/N	0.7657	likely_pathogenic	0.5567	ambiguous	0.162	Stabilizing	0.142	N	0.368	neutral	N	0.472777114	None	None	I
K/P	0.7615	likely_pathogenic	0.542	ambiguous	0.359	Stabilizing	0.998	D	0.732	prob.delet.	None	None	None	None	I
K/Q	0.3075	likely_benign	0.1959	benign	0.013	Stabilizing	0.988	D	0.73	prob.delet.	N	0.477575542	None	None	I
K/R	0.1372	likely_benign	0.1173	benign	-0.111	Destabilizing	0.958	D	0.638	neutral	N	0.479757947	None	None	I
K/S	0.7798	likely_pathogenic	0.5655	pathogenic	-0.336	Destabilizing	0.938	D	0.652	neutral	None	None	None	None	I
K/T	0.5221	ambiguous	0.3245	benign	-0.152	Destabilizing	0.988	D	0.695	prob.neutral	N	0.47865899	None	None	I
K/V	0.5794	likely_pathogenic	0.3812	ambiguous	0.359	Stabilizing	0.995	D	0.718	prob.delet.	None	None	None	None	I
K/W	0.9443	likely_pathogenic	0.8698	pathogenic	-0.125	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
K/Y	0.8538	likely_pathogenic	0.7229	pathogenic	0.21	Stabilizing	0.998	D	0.736	prob.delet.	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.