TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16843	50752;50753;50754	chr2:178611782;178611781;178611780	chr2:179476509;179476508;179476507
N2AB	15202	45829;45830;45831	chr2:178611782;178611781;178611780	chr2:179476509;179476508;179476507
N2A	14275	43048;43049;43050	chr2:178611782;178611781;178611780	chr2:179476509;179476508;179476507
N2B	7778	23557;23558;23559	chr2:178611782;178611781;178611780	chr2:179476509;179476508;179476507
Novex-1	7903	23932;23933;23934	chr2:178611782;178611781;178611780	chr2:179476509;179476508;179476507
Novex-2	7970	24133;24134;24135	chr2:178611782;178611781;178611780	chr2:179476509;179476508;179476507
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-10
• Domain position: 93
• Structural Position: 126
• Q(SASA): 0.2779
• 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
I/N	None	None	0.177	N	0.757	0.311	0.684318996799	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
I/A	0.49	ambiguous	0.519	ambiguous	-1.227	Destabilizing	0.016	N	0.465	neutral	None	None	None	None	N
I/C	0.7234	likely_pathogenic	0.7718	pathogenic	-0.783	Destabilizing	0.869	D	0.54	neutral	None	None	None	None	N
I/D	0.8014	likely_pathogenic	0.784	pathogenic	-0.563	Destabilizing	0.221	N	0.742	deleterious	None	None	None	None	N
I/E	0.7318	likely_pathogenic	0.7365	pathogenic	-0.617	Destabilizing	0.366	N	0.728	deleterious	None	None	None	None	N
I/F	0.1821	likely_benign	0.1917	benign	-0.936	Destabilizing	0.097	N	0.505	neutral	N	0.466536123	None	None	N
I/G	0.7519	likely_pathogenic	0.7759	pathogenic	-1.472	Destabilizing	None	N	0.477	neutral	None	None	None	None	N
I/H	0.6654	likely_pathogenic	0.6657	pathogenic	-0.622	Destabilizing	0.869	D	0.725	deleterious	None	None	None	None	N
I/K	0.6575	likely_pathogenic	0.6353	pathogenic	-0.776	Destabilizing	0.221	N	0.729	deleterious	None	None	None	None	N
I/L	0.0763	likely_benign	0.1092	benign	-0.665	Destabilizing	None	N	0.094	neutral	N	0.464467617	None	None	N
I/M	0.1	likely_benign	0.1092	benign	-0.547	Destabilizing	0.005	N	0.333	neutral	N	0.475445194	None	None	N
I/N	0.3804	ambiguous	0.3541	ambiguous	-0.527	Destabilizing	0.177	N	0.757	deleterious	N	0.470597265	None	None	N
I/P	0.5942	likely_pathogenic	0.5986	pathogenic	-0.819	Destabilizing	0.366	N	0.756	deleterious	None	None	None	None	N
I/Q	0.6231	likely_pathogenic	0.6462	pathogenic	-0.765	Destabilizing	0.366	N	0.745	deleterious	None	None	None	None	N
I/R	0.6128	likely_pathogenic	0.5832	pathogenic	-0.136	Destabilizing	0.366	N	0.755	deleterious	None	None	None	None	N
I/S	0.4679	ambiguous	0.4651	ambiguous	-1.083	Destabilizing	0.03	N	0.647	neutral	N	0.471545047	None	None	N
I/T	0.3764	ambiguous	0.3781	ambiguous	-1.028	Destabilizing	0.058	N	0.591	neutral	N	0.471082711	None	None	N
I/V	0.0995	likely_benign	0.1022	benign	-0.819	Destabilizing	None	N	0.163	neutral	N	0.461277621	None	None	N
I/W	0.7605	likely_pathogenic	0.8152	pathogenic	-0.928	Destabilizing	0.869	D	0.751	deleterious	None	None	None	None	N
I/Y	0.5387	ambiguous	0.5847	pathogenic	-0.72	Destabilizing	0.366	N	0.586	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.