TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20550	61873;61874;61875	chr2:178590077;178590076;178590075	chr2:179454804;179454803;179454802
N2AB	18909	56950;56951;56952	chr2:178590077;178590076;178590075	chr2:179454804;179454803;179454802
N2A	17982	54169;54170;54171	chr2:178590077;178590076;178590075	chr2:179454804;179454803;179454802
N2B	11485	34678;34679;34680	chr2:178590077;178590076;178590075	chr2:179454804;179454803;179454802
Novex-1	11610	35053;35054;35055	chr2:178590077;178590076;178590075	chr2:179454804;179454803;179454802
Novex-2	11677	35254;35255;35256	chr2:178590077;178590076;178590075	chr2:179454804;179454803;179454802
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-121
• Domain position: 72
• Structural Position: 157
• Q(SASA): 0.2165
• 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
S/L	rs2049883330	None	0.001	N	0.423	0.188	0.428401797576	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/L	rs2049883330	None	0.001	N	0.423	0.188	0.428401797576	gnomAD-4.0.0	6.57704E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47111E-05	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
S/A	0.0767	likely_benign	0.0805	benign	-0.564	Destabilizing	None	N	0.167	neutral	N	0.492268927	None	None	N
S/C	0.1085	likely_benign	0.1163	benign	-0.476	Destabilizing	0.901	D	0.563	neutral	None	None	None	None	N
S/D	0.5447	ambiguous	0.6441	pathogenic	-1.491	Destabilizing	0.561	D	0.475	neutral	None	None	None	None	N
S/E	0.5419	ambiguous	0.6356	pathogenic	-1.352	Destabilizing	0.345	N	0.454	neutral	None	None	None	None	N
S/F	0.1629	likely_benign	0.2044	benign	-0.425	Destabilizing	0.818	D	0.628	neutral	None	None	None	None	N
S/G	0.1704	likely_benign	0.186	benign	-0.928	Destabilizing	0.209	N	0.421	neutral	None	None	None	None	N
S/H	0.2872	likely_benign	0.3395	benign	-1.505	Destabilizing	0.965	D	0.567	neutral	None	None	None	None	N
S/I	0.1345	likely_benign	0.1622	benign	0.334	Stabilizing	0.39	N	0.547	neutral	None	None	None	None	N
S/K	0.7128	likely_pathogenic	0.8038	pathogenic	-0.527	Destabilizing	0.007	N	0.187	neutral	None	None	None	None	N
S/L	0.081	likely_benign	0.0954	benign	0.334	Stabilizing	0.001	N	0.423	neutral	N	0.448614151	None	None	N
S/M	0.1395	likely_benign	0.1548	benign	0.364	Stabilizing	0.818	D	0.567	neutral	None	None	None	None	N
S/N	0.1707	likely_benign	0.1993	benign	-1.062	Destabilizing	0.561	D	0.487	neutral	None	None	None	None	N
S/P	0.9734	likely_pathogenic	0.9815	pathogenic	0.07	Stabilizing	0.662	D	0.537	neutral	N	0.485972726	None	None	N
S/Q	0.4766	ambiguous	0.5215	ambiguous	-0.895	Destabilizing	0.561	D	0.54	neutral	None	None	None	None	N
S/R	0.6354	likely_pathogenic	0.7368	pathogenic	-0.838	Destabilizing	0.39	N	0.52	neutral	None	None	None	None	N
S/T	0.0686	likely_benign	0.0724	benign	-0.7	Destabilizing	0.002	N	0.176	neutral	N	0.389141773	None	None	N
S/V	0.1428	likely_benign	0.1601	benign	0.07	Stabilizing	0.209	N	0.549	neutral	None	None	None	None	N
S/W	0.33	likely_benign	0.4106	ambiguous	-0.745	Destabilizing	0.991	D	0.634	neutral	None	None	None	None	N
S/Y	0.16	likely_benign	0.2001	benign	-0.309	Destabilizing	0.901	D	0.619	neutral	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.