TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35688	107287;107288;107289	chr2:178528689;178528688;178528687	chr2:179393416;179393415;179393414
N2AB	34047	102364;102365;102366	chr2:178528689;178528688;178528687	chr2:179393416;179393415;179393414
N2A	33120	99583;99584;99585	chr2:178528689;178528688;178528687	chr2:179393416;179393415;179393414
N2B	26623	80092;80093;80094	chr2:178528689;178528688;178528687	chr2:179393416;179393415;179393414
Novex-1	26748	80467;80468;80469	chr2:178528689;178528688;178528687	chr2:179393416;179393415;179393414
Novex-2	26815	80668;80669;80670	chr2:178528689;178528688;178528687	chr2:179393416;179393415;179393414
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-167
• Domain position: 82
• Structural Position: 169
• Q(SASA): 0.2208
• 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
C/S	rs878952929	-1.487	0.22	N	0.683	0.377	0.696184535837	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.49E-05	0	None	0	0	None	0	None	0	0	0
C/S	rs878952929	-1.487	0.22	N	0.683	0.377	0.696184535837	gnomAD-4.0.0	1.59203E-06	None	None	None	None	N	None	5.65291E-05	0	None	0	0	None	0	0	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
C/A	0.8145	likely_pathogenic	0.8206	pathogenic	-1.758	Destabilizing	0.133	N	0.584	neutral	None	None	None	None	N
C/D	0.9752	likely_pathogenic	0.9811	pathogenic	-0.666	Destabilizing	0.726	D	0.799	deleterious	None	None	None	None	N
C/E	0.982	likely_pathogenic	0.9854	pathogenic	-0.489	Destabilizing	0.726	D	0.801	deleterious	None	None	None	None	N
C/F	0.4574	ambiguous	0.4398	ambiguous	-1.115	Destabilizing	0.331	N	0.718	prob.delet.	N	0.460639298	None	None	N
C/G	0.5789	likely_pathogenic	0.5925	pathogenic	-2.104	Highly Destabilizing	0.667	D	0.739	prob.delet.	N	0.479225059	None	None	N
C/H	0.9047	likely_pathogenic	0.9145	pathogenic	-2.236	Highly Destabilizing	0.832	D	0.785	deleterious	None	None	None	None	N
C/I	0.7904	likely_pathogenic	0.7764	pathogenic	-0.842	Destabilizing	0.567	D	0.709	prob.delet.	None	None	None	None	N
C/K	0.9818	likely_pathogenic	0.9837	pathogenic	-0.867	Destabilizing	0.567	D	0.785	deleterious	None	None	None	None	N
C/L	0.7504	likely_pathogenic	0.7277	pathogenic	-0.842	Destabilizing	0.157	N	0.606	neutral	None	None	None	None	N
C/M	0.8618	likely_pathogenic	0.8576	pathogenic	0.051	Stabilizing	0.909	D	0.719	prob.delet.	None	None	None	None	N
C/N	0.9108	likely_pathogenic	0.9289	pathogenic	-1.143	Destabilizing	0.726	D	0.803	deleterious	None	None	None	None	N
C/P	0.9969	likely_pathogenic	0.9973	pathogenic	-1.123	Destabilizing	0.89	D	0.804	deleterious	None	None	None	None	N
C/Q	0.9523	likely_pathogenic	0.9585	pathogenic	-0.853	Destabilizing	0.726	D	0.805	deleterious	None	None	None	None	N
C/R	0.9109	likely_pathogenic	0.9177	pathogenic	-1.099	Destabilizing	0.497	N	0.805	deleterious	N	0.478704984	None	None	N
C/S	0.7333	likely_pathogenic	0.7571	pathogenic	-1.609	Destabilizing	0.22	N	0.683	prob.neutral	N	0.477144759	None	None	N
C/T	0.818	likely_pathogenic	0.8291	pathogenic	-1.235	Destabilizing	0.567	D	0.7	prob.neutral	None	None	None	None	N
C/V	0.7333	likely_pathogenic	0.7279	pathogenic	-1.123	Destabilizing	0.272	N	0.641	neutral	None	None	None	None	N
C/W	0.8381	likely_pathogenic	0.8433	pathogenic	-1.273	Destabilizing	0.883	D	0.745	deleterious	N	0.479745134	None	None	N
C/Y	0.6468	likely_pathogenic	0.6556	pathogenic	-1.166	Destabilizing	0.001	N	0.536	neutral	N	0.479398418	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.