TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29225	87898;87899;87900	chr2:178557681;178557680;178557679	chr2:179422408;179422407;179422406
N2AB	27584	82975;82976;82977	chr2:178557681;178557680;178557679	chr2:179422408;179422407;179422406
N2A	26657	80194;80195;80196	chr2:178557681;178557680;178557679	chr2:179422408;179422407;179422406
N2B	20160	60703;60704;60705	chr2:178557681;178557680;178557679	chr2:179422408;179422407;179422406
Novex-1	20285	61078;61079;61080	chr2:178557681;178557680;178557679	chr2:179422408;179422407;179422406
Novex-2	20352	61279;61280;61281	chr2:178557681;178557680;178557679	chr2:179422408;179422407;179422406
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-100
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.8862
• Predicted PPI site: I

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
D/Y	None	None	1.0	N	0.786	0.468	0.733514829897	gnomAD-4.0.0	2.05251E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69827E-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
D/A	0.5206	ambiguous	0.6251	pathogenic	-0.518	Destabilizing	1.0	D	0.729	deleterious	N	0.50605937	None	None	I
D/C	0.873	likely_pathogenic	0.9216	pathogenic	-0.307	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
D/E	0.3907	ambiguous	0.4515	ambiguous	-0.784	Destabilizing	0.999	D	0.542	neutral	N	0.42734787	None	None	I
D/F	0.8785	likely_pathogenic	0.9196	pathogenic	0.012	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
D/G	0.6607	likely_pathogenic	0.7471	pathogenic	-0.928	Destabilizing	1.0	D	0.745	deleterious	N	0.483154207	None	None	I
D/H	0.7214	likely_pathogenic	0.7936	pathogenic	-0.393	Destabilizing	1.0	D	0.763	deleterious	N	0.477927194	None	None	I
D/I	0.5924	likely_pathogenic	0.7049	pathogenic	0.588	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
D/K	0.8669	likely_pathogenic	0.9078	pathogenic	-0.749	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
D/L	0.69	likely_pathogenic	0.7706	pathogenic	0.588	Stabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
D/M	0.868	likely_pathogenic	0.9192	pathogenic	1.094	Stabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
D/N	0.2298	likely_benign	0.3071	benign	-1.209	Destabilizing	1.0	D	0.675	prob.neutral	N	0.518719236	None	None	I
D/P	0.8999	likely_pathogenic	0.9418	pathogenic	0.245	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
D/Q	0.7795	likely_pathogenic	0.8481	pathogenic	-0.986	Destabilizing	1.0	D	0.616	neutral	None	None	None	None	I
D/R	0.8772	likely_pathogenic	0.9168	pathogenic	-0.569	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
D/S	0.319	likely_benign	0.4193	ambiguous	-1.546	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
D/T	0.4563	ambiguous	0.5726	pathogenic	-1.203	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
D/V	0.4055	ambiguous	0.5178	ambiguous	0.245	Stabilizing	1.0	D	0.769	deleterious	N	0.485454811	None	None	I
D/W	0.9813	likely_pathogenic	0.9881	pathogenic	0.125	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
D/Y	0.6014	likely_pathogenic	0.6846	pathogenic	0.226	Stabilizing	1.0	D	0.786	deleterious	N	0.496284939	None	None	I

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.