TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22963	69112;69113;69114	chr2:178577448;178577447;178577446	chr2:179442175;179442174;179442173
N2AB	21322	64189;64190;64191	chr2:178577448;178577447;178577446	chr2:179442175;179442174;179442173
N2A	20395	61408;61409;61410	chr2:178577448;178577447;178577446	chr2:179442175;179442174;179442173
N2B	13898	41917;41918;41919	chr2:178577448;178577447;178577446	chr2:179442175;179442174;179442173
Novex-1	14023	42292;42293;42294	chr2:178577448;178577447;178577446	chr2:179442175;179442174;179442173
Novex-2	14090	42493;42494;42495	chr2:178577448;178577447;178577446	chr2:179442175;179442174;179442173
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-128
• Domain position: 14
• Structural Position: 26
• Q(SASA): 0.2497
• 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
T/P	rs771761816	-0.547	0.638	N	0.429	0.317	0.327419511103	gnomAD-2.1.1	4.46E-05	None	None	None	None	I	None	0	2.90529E-04	None	0	0	None	0	None	0	0	1.67448E-04
T/P	rs771761816	-0.547	0.638	N	0.429	0.317	0.327419511103	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
T/P	rs771761816	-0.547	0.638	N	0.429	0.317	0.327419511103	gnomAD-4.0.0	1.12024E-05	None	None	None	None	I	None	1.33469E-05	2.33754E-04	None	0	0	None	0	0	2.55204E-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
T/A	0.0913	likely_benign	0.0923	benign	-0.894	Destabilizing	0.094	N	0.431	neutral	N	0.489283684	None	None	I
T/C	0.4123	ambiguous	0.4363	ambiguous	-0.551	Destabilizing	0.947	D	0.474	neutral	None	None	None	None	I
T/D	0.3237	likely_benign	0.3426	ambiguous	-0.053	Destabilizing	0.25	N	0.397	neutral	None	None	None	None	I
T/E	0.3617	ambiguous	0.375	ambiguous	-0.025	Destabilizing	0.25	N	0.387	neutral	None	None	None	None	I
T/F	0.3606	ambiguous	0.349	ambiguous	-0.906	Destabilizing	0.826	D	0.568	neutral	None	None	None	None	I
T/G	0.286	likely_benign	0.2992	benign	-1.178	Destabilizing	0.25	N	0.455	neutral	None	None	None	None	I
T/H	0.3118	likely_benign	0.3132	benign	-1.381	Destabilizing	0.898	D	0.567	neutral	None	None	None	None	I
T/I	0.2166	likely_benign	0.1909	benign	-0.22	Destabilizing	0.638	D	0.432	neutral	N	0.472545829	None	None	I
T/K	0.3124	likely_benign	0.3231	benign	-0.64	Destabilizing	0.25	N	0.41	neutral	None	None	None	None	I
T/L	0.141	likely_benign	0.1292	benign	-0.22	Destabilizing	0.399	N	0.403	neutral	None	None	None	None	I
T/M	0.1066	likely_benign	0.1018	benign	0.019	Stabilizing	0.982	D	0.448	neutral	None	None	None	None	I
T/N	0.0991	likely_benign	0.1034	benign	-0.678	Destabilizing	0.004	N	0.267	neutral	N	0.500095324	None	None	I
T/P	0.1511	likely_benign	0.1504	benign	-0.412	Destabilizing	0.638	D	0.429	neutral	N	0.489859688	None	None	I
T/Q	0.304	likely_benign	0.3117	benign	-0.777	Destabilizing	0.7	D	0.439	neutral	None	None	None	None	I
T/R	0.2816	likely_benign	0.2987	benign	-0.472	Destabilizing	0.7	D	0.44	neutral	None	None	None	None	I
T/S	0.1028	likely_benign	0.1074	benign	-1.021	Destabilizing	0.002	N	0.263	neutral	N	0.482912286	None	None	I
T/V	0.1533	likely_benign	0.1369	benign	-0.412	Destabilizing	0.399	N	0.403	neutral	None	None	None	None	I
T/W	0.7581	likely_pathogenic	0.7784	pathogenic	-0.83	Destabilizing	0.982	D	0.613	neutral	None	None	None	None	I
T/Y	0.3652	ambiguous	0.3784	ambiguous	-0.587	Destabilizing	0.826	D	0.568	neutral	None	None	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.