TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27698	83317;83318;83319	chr2:178563040;178563039;178563038	chr2:179427767;179427766;179427765
N2AB	26057	78394;78395;78396	chr2:178563040;178563039;178563038	chr2:179427767;179427766;179427765
N2A	25130	75613;75614;75615	chr2:178563040;178563039;178563038	chr2:179427767;179427766;179427765
N2B	18633	56122;56123;56124	chr2:178563040;178563039;178563038	chr2:179427767;179427766;179427765
Novex-1	18758	56497;56498;56499	chr2:178563040;178563039;178563038	chr2:179427767;179427766;179427765
Novex-2	18825	56698;56699;56700	chr2:178563040;178563039;178563038	chr2:179427767;179427766;179427765
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-141
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.169
• 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/A	None	None	0.656	N	0.529	0.219	0.365703291355	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
T/A	0.0881	likely_benign	0.1035	benign	-0.833	Destabilizing	0.656	D	0.529	neutral	N	0.50333407	None	None	N
T/C	0.4663	ambiguous	0.5274	ambiguous	-0.448	Destabilizing	0.998	D	0.68	prob.neutral	None	None	None	None	N
T/D	0.6881	likely_pathogenic	0.7219	pathogenic	0.108	Stabilizing	0.978	D	0.662	neutral	None	None	None	None	N
T/E	0.581	likely_pathogenic	0.6173	pathogenic	0.195	Stabilizing	0.978	D	0.654	neutral	None	None	None	None	N
T/F	0.4921	ambiguous	0.5764	pathogenic	-0.706	Destabilizing	0.956	D	0.747	deleterious	None	None	None	None	N
T/G	0.2733	likely_benign	0.3107	benign	-1.159	Destabilizing	0.926	D	0.693	prob.neutral	None	None	None	None	N
T/H	0.3487	ambiguous	0.3966	ambiguous	-1.237	Destabilizing	0.998	D	0.732	prob.delet.	None	None	None	None	N
T/I	0.2826	likely_benign	0.3315	benign	-0.031	Destabilizing	0.032	N	0.387	neutral	N	0.512185627	None	None	N
T/K	0.2948	likely_benign	0.3253	benign	-0.304	Destabilizing	0.978	D	0.661	neutral	None	None	None	None	N
T/L	0.1482	likely_benign	0.1741	benign	-0.031	Destabilizing	0.514	D	0.574	neutral	None	None	None	None	N
T/M	0.1139	likely_benign	0.1351	benign	-0.062	Destabilizing	0.988	D	0.679	prob.neutral	None	None	None	None	N
T/N	0.1613	likely_benign	0.1761	benign	-0.496	Destabilizing	0.99	D	0.565	neutral	N	0.49633074	None	None	N
T/P	0.07	likely_benign	0.0754	benign	-0.266	Destabilizing	0.014	N	0.323	neutral	N	0.404442086	None	None	N
T/Q	0.2951	likely_benign	0.3321	benign	-0.464	Destabilizing	0.993	D	0.695	prob.neutral	None	None	None	None	N
T/R	0.2837	likely_benign	0.3145	benign	-0.29	Destabilizing	0.993	D	0.692	prob.neutral	None	None	None	None	N
T/S	0.1437	likely_benign	0.1657	benign	-0.865	Destabilizing	0.904	D	0.512	neutral	N	0.468682779	None	None	N
T/V	0.1898	likely_benign	0.2235	benign	-0.266	Destabilizing	0.514	D	0.519	neutral	None	None	None	None	N
T/W	0.8033	likely_pathogenic	0.8395	pathogenic	-0.686	Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	N
T/Y	0.4845	ambiguous	0.5138	ambiguous	-0.386	Destabilizing	0.978	D	0.745	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.