TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21913	65962;65963;65964	chr2:178583066;178583065;178583064	chr2:179447793;179447792;179447791
N2AB	20272	61039;61040;61041	chr2:178583066;178583065;178583064	chr2:179447793;179447792;179447791
N2A	19345	58258;58259;58260	chr2:178583066;178583065;178583064	chr2:179447793;179447792;179447791
N2B	12848	38767;38768;38769	chr2:178583066;178583065;178583064	chr2:179447793;179447792;179447791
Novex-1	12973	39142;39143;39144	chr2:178583066;178583065;178583064	chr2:179447793;179447792;179447791
Novex-2	13040	39343;39344;39345	chr2:178583066;178583065;178583064	chr2:179447793;179447792;179447791
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: Ig-125
• Domain position: 48
• Structural Position: 125
• Q(SASA): 0.475
• 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
A/S	None	None	0.045	N	0.199	0.119	0.221734844693	gnomAD-4.0.0	1.37071E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.73732E-04	9.00486E-07	0	0
A/V	rs751046277	0.101	0.002	N	0.075	0.083	0.273070737957	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	3.16456E-03	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
A/C	0.3717	ambiguous	0.3579	ambiguous	-0.337	Destabilizing	0.992	D	0.396	neutral	None	None	None	None	I
A/D	0.2202	likely_benign	0.2205	benign	-1.229	Destabilizing	0.004	N	0.299	neutral	N	0.429412314	None	None	I
A/E	0.1988	likely_benign	0.1972	benign	-1.378	Destabilizing	0.447	N	0.361	neutral	None	None	None	None	I
A/F	0.248	likely_benign	0.2398	benign	-1.081	Destabilizing	0.85	D	0.477	neutral	None	None	None	None	I
A/G	0.1316	likely_benign	0.1257	benign	-0.551	Destabilizing	0.334	N	0.28	neutral	N	0.462140808	None	None	I
A/H	0.2778	likely_benign	0.2755	benign	-0.884	Destabilizing	0.992	D	0.435	neutral	None	None	None	None	I
A/I	0.1731	likely_benign	0.1629	benign	-0.373	Destabilizing	0.005	N	0.212	neutral	None	None	None	None	I
A/K	0.2655	likely_benign	0.2668	benign	-0.939	Destabilizing	0.617	D	0.388	neutral	None	None	None	None	I
A/L	0.149	likely_benign	0.1408	benign	-0.373	Destabilizing	0.103	N	0.349	neutral	None	None	None	None	I
A/M	0.1798	likely_benign	0.1685	benign	-0.114	Destabilizing	0.85	D	0.412	neutral	None	None	None	None	I
A/N	0.1389	likely_benign	0.1376	benign	-0.351	Destabilizing	0.447	N	0.458	neutral	None	None	None	None	I
A/P	0.7093	likely_pathogenic	0.6983	pathogenic	-0.366	Destabilizing	0.896	D	0.423	neutral	N	0.47335788	None	None	I
A/Q	0.2243	likely_benign	0.2219	benign	-0.688	Destabilizing	0.92	D	0.424	neutral	None	None	None	None	I
A/R	0.2543	likely_benign	0.2585	benign	-0.435	Destabilizing	0.92	D	0.433	neutral	None	None	None	None	I
A/S	0.0817	likely_benign	0.0811	benign	-0.416	Destabilizing	0.045	N	0.199	neutral	N	0.385352106	None	None	I
A/T	0.0681	likely_benign	0.0654	benign	-0.517	Destabilizing	0.007	N	0.071	neutral	N	0.386274826	None	None	I
A/V	0.1009	likely_benign	0.096	benign	-0.366	Destabilizing	0.002	N	0.075	neutral	N	0.400841633	None	None	I
A/W	0.6073	likely_pathogenic	0.6154	pathogenic	-1.299	Destabilizing	0.992	D	0.523	neutral	None	None	None	None	I
A/Y	0.3366	likely_benign	0.338	benign	-0.966	Destabilizing	0.92	D	0.477	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.