TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6162	18709;18710;18711	chr2:178729769;178729768;178729767	chr2:179594496;179594495;179594494
N2AB	5845	17758;17759;17760	chr2:178729769;178729768;178729767	chr2:179594496;179594495;179594494
N2A	4918	14977;14978;14979	chr2:178729769;178729768;178729767	chr2:179594496;179594495;179594494
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-45
• Domain position: 58
• Structural Position: 137
• Q(SASA): 0.1846
• 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
T/I	rs367685188	0.172	0.497	D	0.679	0.345	None	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	1.24008E-04	0	None	0	0	None	0	None	0	0	0
T/I	rs367685188	0.172	0.497	D	0.679	0.345	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.20616E-04	0	0	0	0	None	0	0	0	0	0
T/I	rs367685188	0.172	0.497	D	0.679	0.345	None	gnomAD-4.0.0	6.0897E-06	None	None	None	None	N	None	1.04822E-04	0	None	0	0	None	0	0	0	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
T/A	0.0775	likely_benign	0.078	benign	-1.195	Destabilizing	0.055	N	0.511	neutral	D	0.524442848	None	None	N
T/C	0.3548	ambiguous	0.3555	ambiguous	-0.885	Destabilizing	0.909	D	0.684	prob.neutral	None	None	None	None	N
T/D	0.3817	ambiguous	0.3623	ambiguous	-1.35	Destabilizing	0.396	N	0.645	neutral	None	None	None	None	N
T/E	0.2534	likely_benign	0.2626	benign	-1.171	Destabilizing	0.157	N	0.617	neutral	None	None	None	None	N
T/F	0.1544	likely_benign	0.159	benign	-0.903	Destabilizing	0.726	D	0.729	prob.delet.	None	None	None	None	N
T/G	0.2527	likely_benign	0.2478	benign	-1.6	Destabilizing	0.157	N	0.593	neutral	None	None	None	None	N
T/H	0.172	likely_benign	0.1784	benign	-1.721	Destabilizing	0.909	D	0.715	prob.delet.	None	None	None	None	N
T/I	0.0985	likely_benign	0.1046	benign	-0.14	Destabilizing	0.497	N	0.679	prob.neutral	D	0.523058768	None	None	N
T/K	0.1362	likely_benign	0.1478	benign	-0.578	Destabilizing	0.157	N	0.567	neutral	None	None	None	None	N
T/L	0.0815	likely_benign	0.0848	benign	-0.14	Destabilizing	0.272	N	0.596	neutral	None	None	None	None	N
T/M	0.0872	likely_benign	0.0911	benign	-0.099	Destabilizing	0.968	D	0.688	prob.neutral	None	None	None	None	N
T/N	0.1192	likely_benign	0.1134	benign	-1.192	Destabilizing	0.124	N	0.582	neutral	D	0.530619459	None	None	N
T/P	0.5029	ambiguous	0.4704	ambiguous	-0.46	Destabilizing	0.497	N	0.679	prob.neutral	D	0.524808718	None	None	N
T/Q	0.1766	likely_benign	0.1863	benign	-1.031	Destabilizing	0.567	D	0.687	prob.neutral	None	None	None	None	N
T/R	0.0947	likely_benign	0.1064	benign	-0.724	Destabilizing	0.003	N	0.373	neutral	None	None	None	None	N
T/S	0.0949	likely_benign	0.0908	benign	-1.442	Destabilizing	0.001	N	0.279	neutral	N	0.444421839	None	None	N
T/V	0.0893	likely_benign	0.0949	benign	-0.46	Destabilizing	0.272	N	0.591	neutral	None	None	None	None	N
T/W	0.464	ambiguous	0.4624	ambiguous	-1.0	Destabilizing	0.968	D	0.706	prob.neutral	None	None	None	None	N
T/Y	0.1792	likely_benign	0.1775	benign	-0.642	Destabilizing	0.726	D	0.73	prob.delet.	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.