TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23485	70678;70679;70680	chr2:178575679;178575678;178575677	chr2:179440406;179440405;179440404
N2AB	21844	65755;65756;65757	chr2:178575679;178575678;178575677	chr2:179440406;179440405;179440404
N2A	20917	62974;62975;62976	chr2:178575679;178575678;178575677	chr2:179440406;179440405;179440404
N2B	14420	43483;43484;43485	chr2:178575679;178575678;178575677	chr2:179440406;179440405;179440404
Novex-1	14545	43858;43859;43860	chr2:178575679;178575678;178575677	chr2:179440406;179440405;179440404
Novex-2	14612	44059;44060;44061	chr2:178575679;178575678;178575677	chr2:179440406;179440405;179440404
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-58
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2314
• 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
A/D	None	None	0.295	N	0.527	0.148	0.117506650769	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
A/C	0.3497	ambiguous	0.3584	ambiguous	-1.0	Destabilizing	0.356	N	0.553	neutral	None	None	None	None	N
A/D	0.6558	likely_pathogenic	0.7047	pathogenic	-0.857	Destabilizing	0.295	N	0.527	neutral	N	0.492391066	None	None	N
A/E	0.4768	ambiguous	0.529	ambiguous	-0.893	Destabilizing	0.136	N	0.495	neutral	None	None	None	None	N
A/F	0.2889	likely_benign	0.2979	benign	-1.076	Destabilizing	0.072	N	0.521	neutral	None	None	None	None	N
A/G	0.2525	likely_benign	0.2574	benign	-1.14	Destabilizing	0.106	N	0.421	neutral	N	0.492564424	None	None	N
A/H	0.672	likely_pathogenic	0.6972	pathogenic	-1.27	Destabilizing	0.864	D	0.525	neutral	None	None	None	None	N
A/I	0.0789	likely_benign	0.0798	benign	-0.385	Destabilizing	None	N	0.261	neutral	None	None	None	None	N
A/K	0.744	likely_pathogenic	0.7902	pathogenic	-1.061	Destabilizing	0.136	N	0.498	neutral	None	None	None	None	N
A/L	0.1065	likely_benign	0.1059	benign	-0.385	Destabilizing	None	N	0.249	neutral	None	None	None	None	N
A/M	0.1275	likely_benign	0.1247	benign	-0.389	Destabilizing	0.214	N	0.524	neutral	None	None	None	None	N
A/N	0.4303	ambiguous	0.4631	ambiguous	-0.819	Destabilizing	0.628	D	0.524	neutral	None	None	None	None	N
A/P	0.7662	likely_pathogenic	0.7707	pathogenic	-0.513	Destabilizing	0.295	N	0.536	neutral	N	0.517596154	None	None	N
A/Q	0.507	ambiguous	0.5458	ambiguous	-0.965	Destabilizing	0.628	D	0.523	neutral	None	None	None	None	N
A/R	0.7106	likely_pathogenic	0.7535	pathogenic	-0.755	Destabilizing	0.356	N	0.525	neutral	None	None	None	None	N
A/S	0.1186	likely_benign	0.1222	benign	-1.212	Destabilizing	0.055	N	0.437	neutral	N	0.48271279	None	None	N
A/T	0.0893	likely_benign	0.0863	benign	-1.141	Destabilizing	0.012	N	0.409	neutral	N	0.476325535	None	None	N
A/V	0.0504	likely_benign	0.0514	benign	-0.513	Destabilizing	None	N	0.163	neutral	N	0.303530438	None	None	N
A/W	0.8563	likely_pathogenic	0.8607	pathogenic	-1.371	Destabilizing	0.864	D	0.585	neutral	None	None	None	None	N
A/Y	0.5703	likely_pathogenic	0.5867	pathogenic	-0.959	Destabilizing	0.356	N	0.517	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.