TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7662	23209;23210;23211	chr2:178721035;178721034;178721033	chr2:179585762;179585761;179585760
N2AB	7345	22258;22259;22260	chr2:178721035;178721034;178721033	chr2:179585762;179585761;179585760
N2A	6418	19477;19478;19479	chr2:178721035;178721034;178721033	chr2:179585762;179585761;179585760
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-61
• Domain position: 55
• Structural Position: 134
• Q(SASA): 0.3198
• 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/A	None	None	0.498	N	0.507	0.269	0.328222422547	gnomAD-4.0.0	1.59238E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4334E-05	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	0.1079	likely_benign	0.1046	benign	-0.544	Destabilizing	0.498	N	0.507	neutral	N	0.481387142	None	None	N
S/C	0.2628	likely_benign	0.2497	benign	-0.319	Destabilizing	0.191	N	0.394	neutral	N	0.511687531	None	None	N
S/D	0.4238	ambiguous	0.553	ambiguous	0.454	Stabilizing	0.956	D	0.567	neutral	None	None	None	None	N
S/E	0.6463	likely_pathogenic	0.7311	pathogenic	0.46	Stabilizing	0.984	D	0.569	neutral	None	None	None	None	N
S/F	0.3684	ambiguous	0.4121	ambiguous	-0.78	Destabilizing	1.0	D	0.755	deleterious	N	0.490607535	None	None	N
S/G	0.0857	likely_benign	0.1094	benign	-0.788	Destabilizing	0.988	D	0.538	neutral	None	None	None	None	N
S/H	0.4281	ambiguous	0.5073	ambiguous	-1.184	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
S/I	0.5434	ambiguous	0.5887	pathogenic	-0.009	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
S/K	0.7796	likely_pathogenic	0.8495	pathogenic	-0.299	Destabilizing	0.994	D	0.573	neutral	None	None	None	None	N
S/L	0.1675	likely_benign	0.1618	benign	-0.009	Destabilizing	0.994	D	0.685	prob.neutral	None	None	None	None	N
S/M	0.3027	likely_benign	0.312	benign	0.02	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
S/N	0.1568	likely_benign	0.2369	benign	-0.294	Destabilizing	0.063	N	0.282	neutral	None	None	None	None	N
S/P	0.7589	likely_pathogenic	0.8065	pathogenic	-0.153	Destabilizing	0.999	D	0.691	prob.neutral	N	0.499824247	None	None	N
S/Q	0.5891	likely_pathogenic	0.6518	pathogenic	-0.346	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
S/R	0.7149	likely_pathogenic	0.7935	pathogenic	-0.31	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
S/T	0.1328	likely_benign	0.1478	benign	-0.343	Destabilizing	0.792	D	0.566	neutral	N	0.507315738	None	None	N
S/V	0.4645	ambiguous	0.4779	ambiguous	-0.153	Destabilizing	0.995	D	0.689	prob.neutral	None	None	None	None	N
S/W	0.4764	ambiguous	0.552	ambiguous	-0.792	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
S/Y	0.2498	likely_benign	0.2984	benign	-0.478	Destabilizing	1.0	D	0.75	deleterious	D	0.523997344	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.