TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6297	19114;19115;19116	chr2:178729149;178729148;178729147	chr2:179593876;179593875;179593874
N2AB	5980	18163;18164;18165	chr2:178729149;178729148;178729147	chr2:179593876;179593875;179593874
N2A	5053	15382;15383;15384	chr2:178729149;178729148;178729147	chr2:179593876;179593875;179593874
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-47
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.6521
• 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/E	None	None	0.124	N	0.555	0.281	0.369867359543	gnomAD-4.0.0	1.6573E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.95933E-06	0	0
K/R	rs1208730507	None	0.001	D	0.187	0.126	0.269111216191	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs1208730507	None	0.001	D	0.187	0.126	0.269111216191	gnomAD-4.0.0	2.02988E-06	None	None	None	None	I	None	1.74672E-05	0	None	0	0	None	0	0	1.20493E-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	0.6488	likely_pathogenic	0.5916	pathogenic	-0.612	Destabilizing	0.272	N	0.597	neutral	None	None	None	None	I
K/C	0.9004	likely_pathogenic	0.8882	pathogenic	-0.621	Destabilizing	0.968	D	0.728	prob.delet.	None	None	None	None	I
K/D	0.8034	likely_pathogenic	0.7651	pathogenic	0.343	Stabilizing	0.567	D	0.612	neutral	None	None	None	None	I
K/E	0.4041	ambiguous	0.3609	ambiguous	0.459	Stabilizing	0.124	N	0.555	neutral	N	0.484251206	None	None	I
K/F	0.9264	likely_pathogenic	0.9049	pathogenic	-0.294	Destabilizing	0.726	D	0.71	prob.delet.	None	None	None	None	I
K/G	0.6956	likely_pathogenic	0.6523	pathogenic	-0.964	Destabilizing	0.272	N	0.58	neutral	None	None	None	None	I
K/H	0.5155	ambiguous	0.4729	ambiguous	-1.152	Destabilizing	0.909	D	0.664	neutral	None	None	None	None	I
K/I	0.7032	likely_pathogenic	0.6614	pathogenic	0.294	Stabilizing	0.567	D	0.711	prob.delet.	None	None	None	None	I
K/L	0.6645	likely_pathogenic	0.6144	pathogenic	0.294	Stabilizing	0.272	N	0.583	neutral	None	None	None	None	I
K/M	0.4187	ambiguous	0.3997	ambiguous	0.078	Stabilizing	0.958	D	0.661	neutral	D	0.534920348	None	None	I
K/N	0.6131	likely_pathogenic	0.5747	pathogenic	-0.236	Destabilizing	0.497	N	0.56	neutral	N	0.498938874	None	None	I
K/P	0.6764	likely_pathogenic	0.653	pathogenic	0.022	Stabilizing	0.726	D	0.665	neutral	None	None	None	None	I
K/Q	0.2322	likely_benign	0.2155	benign	-0.299	Destabilizing	0.497	N	0.591	neutral	N	0.489442219	None	None	I
K/R	0.1037	likely_benign	0.0962	benign	-0.347	Destabilizing	0.001	N	0.187	neutral	D	0.527672367	None	None	I
K/S	0.7221	likely_pathogenic	0.6738	pathogenic	-1.004	Destabilizing	0.157	N	0.522	neutral	None	None	None	None	I
K/T	0.4095	ambiguous	0.3512	ambiguous	-0.677	Destabilizing	0.009	N	0.29	neutral	D	0.534406338	None	None	I
K/V	0.6582	likely_pathogenic	0.6109	pathogenic	0.022	Stabilizing	0.567	D	0.581	neutral	None	None	None	None	I
K/W	0.9103	likely_pathogenic	0.8882	pathogenic	-0.119	Destabilizing	0.968	D	0.735	prob.delet.	None	None	None	None	I
K/Y	0.8076	likely_pathogenic	0.7674	pathogenic	0.161	Stabilizing	0.726	D	0.709	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.