TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14706	44341;44342;44343	chr2:178630842;178630841;178630840	chr2:179495569;179495568;179495567
N2AB	13065	39418;39419;39420	chr2:178630842;178630841;178630840	chr2:179495569;179495568;179495567
N2A	12138	36637;36638;36639	chr2:178630842;178630841;178630840	chr2:179495569;179495568;179495567
N2B	5641	17146;17147;17148	chr2:178630842;178630841;178630840	chr2:179495569;179495568;179495567
Novex-1	5766	17521;17522;17523	chr2:178630842;178630841;178630840	chr2:179495569;179495568;179495567
Novex-2	5833	17722;17723;17724	chr2:178630842;178630841;178630840	chr2:179495569;179495568;179495567
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-98
• Domain position: 32
• Structural Position: 47
• Q(SASA): 0.543
• 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
N/S	rs878854309	-0.608	0.001	N	0.202	0.086	0.0551355673512	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14705E-04	0	None	0	0	None	0	None	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
N/A	0.2065	likely_benign	0.192	benign	-0.759	Destabilizing	0.002	N	0.367	neutral	None	None	None	None	N
N/C	0.2586	likely_benign	0.2547	benign	0.098	Stabilizing	0.878	D	0.461	neutral	None	None	None	None	N
N/D	0.1862	likely_benign	0.198	benign	-0.081	Destabilizing	0.094	N	0.393	neutral	N	0.434971343	None	None	N
N/E	0.4142	ambiguous	0.4237	ambiguous	-0.015	Destabilizing	0.064	N	0.375	neutral	None	None	None	None	N
N/F	0.4375	ambiguous	0.4388	ambiguous	-0.693	Destabilizing	0.538	D	0.586	neutral	None	None	None	None	N
N/G	0.3255	likely_benign	0.3129	benign	-1.05	Destabilizing	0.064	N	0.317	neutral	None	None	None	None	N
N/H	0.1001	likely_benign	0.0981	benign	-0.82	Destabilizing	0.002	N	0.253	neutral	N	0.409485672	None	None	N
N/I	0.1395	likely_benign	0.1305	benign	-0.038	Destabilizing	None	N	0.405	neutral	N	0.405579298	None	None	N
N/K	0.296	likely_benign	0.3074	benign	-0.193	Destabilizing	0.049	N	0.392	neutral	N	0.425702127	None	None	N
N/L	0.196	likely_benign	0.1931	benign	-0.038	Destabilizing	0.064	N	0.349	neutral	None	None	None	None	N
N/M	0.2854	likely_benign	0.2733	benign	0.202	Stabilizing	0.538	D	0.499	neutral	None	None	None	None	N
N/P	0.7911	likely_pathogenic	0.8301	pathogenic	-0.25	Destabilizing	0.403	N	0.531	neutral	None	None	None	None	N
N/Q	0.3211	likely_benign	0.3192	benign	-0.557	Destabilizing	0.013	N	0.281	neutral	None	None	None	None	N
N/R	0.309	likely_benign	0.3214	benign	-0.221	Destabilizing	0.25	N	0.407	neutral	None	None	None	None	N
N/S	0.076	likely_benign	0.0728	benign	-0.618	Destabilizing	0.001	N	0.202	neutral	N	0.397073888	None	None	N
N/T	0.1008	likely_benign	0.089	benign	-0.371	Destabilizing	0.001	N	0.243	neutral	N	0.364698575	None	None	N
N/V	0.1521	likely_benign	0.1424	benign	-0.25	Destabilizing	0.064	N	0.351	neutral	None	None	None	None	N
N/W	0.7342	likely_pathogenic	0.7676	pathogenic	-0.549	Destabilizing	0.964	D	0.503	neutral	None	None	None	None	N
N/Y	0.1479	likely_benign	0.1591	benign	-0.339	Destabilizing	0.468	N	0.606	neutral	N	0.431466875	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.