TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33518	100777;100778;100779	chr2:178536195;178536194;178536193	chr2:179400922;179400921;179400920
N2AB	31877	95854;95855;95856	chr2:178536195;178536194;178536193	chr2:179400922;179400921;179400920
N2A	30950	93073;93074;93075	chr2:178536195;178536194;178536193	chr2:179400922;179400921;179400920
N2B	24453	73582;73583;73584	chr2:178536195;178536194;178536193	chr2:179400922;179400921;179400920
Novex-1	24578	73957;73958;73959	chr2:178536195;178536194;178536193	chr2:179400922;179400921;179400920
Novex-2	24645	74158;74159;74160	chr2:178536195;178536194;178536193	chr2:179400922;179400921;179400920
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: Ig-158
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.1376
• 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
K/R	rs1691428129	None	0.997	N	0.424	0.45	0.415438038341	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs1691428129	None	0.997	N	0.424	0.45	0.415438038341	gnomAD-4.0.0	5.12605E-06	None	None	None	None	N	None	1.6909E-05	0	None	0	0	None	0	0	4.78755E-06	0	2.84527E-05

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	0.9746	likely_pathogenic	0.9691	pathogenic	-1.161	Destabilizing	1.0	D	0.533	neutral	None	None	None	None	N
K/C	0.979	likely_pathogenic	0.9728	pathogenic	-1.298	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/D	0.9964	likely_pathogenic	0.9957	pathogenic	-1.158	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
K/E	0.9743	likely_pathogenic	0.9697	pathogenic	-0.95	Destabilizing	0.997	D	0.473	neutral	N	0.486863108	None	None	N
K/F	0.9953	likely_pathogenic	0.9933	pathogenic	-0.541	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
K/G	0.9876	likely_pathogenic	0.9838	pathogenic	-1.593	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
K/H	0.8655	likely_pathogenic	0.8416	pathogenic	-1.79	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
K/I	0.9722	likely_pathogenic	0.9673	pathogenic	0.019	Stabilizing	0.999	D	0.751	deleterious	D	0.523151982	None	None	N
K/L	0.9602	likely_pathogenic	0.956	pathogenic	0.019	Stabilizing	0.996	D	0.693	prob.neutral	None	None	None	None	N
K/M	0.9306	likely_pathogenic	0.9214	pathogenic	-0.234	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/N	0.9859	likely_pathogenic	0.9834	pathogenic	-1.378	Destabilizing	1.0	D	0.671	neutral	N	0.516455296	None	None	N
K/P	0.9946	likely_pathogenic	0.9931	pathogenic	-0.348	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/Q	0.8276	likely_pathogenic	0.8083	pathogenic	-1.259	Destabilizing	0.956	D	0.318	neutral	N	0.504179432	None	None	N
K/R	0.172	likely_benign	0.1645	benign	-1.067	Destabilizing	0.997	D	0.424	neutral	N	0.479745134	None	None	N
K/S	0.9861	likely_pathogenic	0.9826	pathogenic	-1.982	Destabilizing	1.0	D	0.488	neutral	None	None	None	None	N
K/T	0.9367	likely_pathogenic	0.9274	pathogenic	-1.546	Destabilizing	1.0	D	0.711	prob.delet.	N	0.500272335	None	None	N
K/V	0.9522	likely_pathogenic	0.9454	pathogenic	-0.348	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	N
K/W	0.9925	likely_pathogenic	0.9893	pathogenic	-0.502	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
K/Y	0.9841	likely_pathogenic	0.9798	pathogenic	-0.173	Destabilizing	1.0	D	0.759	deleterious	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.