TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20291	61096;61097;61098	chr2:178590854;178590853;178590852	chr2:179455581;179455580;179455579
N2AB	18650	56173;56174;56175	chr2:178590854;178590853;178590852	chr2:179455581;179455580;179455579
N2A	17723	53392;53393;53394	chr2:178590854;178590853;178590852	chr2:179455581;179455580;179455579
N2B	11226	33901;33902;33903	chr2:178590854;178590853;178590852	chr2:179455581;179455580;179455579
Novex-1	11351	34276;34277;34278	chr2:178590854;178590853;178590852	chr2:179455581;179455580;179455579
Novex-2	11418	34477;34478;34479	chr2:178590854;178590853;178590852	chr2:179455581;179455580;179455579
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-35
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.1986
• 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
S/F	None	None	0.484	N	0.607	0.434	0.63162399683	gnomAD-4.0.0	1.60051E-06	None	None	None	None	N	None	0	0	None	0	2.78956E-05	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
S/A	0.081	likely_benign	0.0755	benign	-0.412	Destabilizing	None	N	0.183	neutral	N	0.501208124	None	None	N
S/C	0.0864	likely_benign	0.0804	benign	-0.247	Destabilizing	0.78	D	0.509	neutral	N	0.477100593	None	None	N
S/D	0.5211	ambiguous	0.4904	ambiguous	-0.382	Destabilizing	0.149	N	0.361	neutral	None	None	None	None	N
S/E	0.4671	ambiguous	0.4347	ambiguous	-0.288	Destabilizing	0.149	N	0.362	neutral	None	None	None	None	N
S/F	0.1621	likely_benign	0.1581	benign	-0.404	Destabilizing	0.484	N	0.607	neutral	N	0.500876387	None	None	N
S/G	0.1068	likely_benign	0.101	benign	-0.744	Destabilizing	None	N	0.152	neutral	None	None	None	None	N
S/H	0.3054	likely_benign	0.2891	benign	-1.26	Destabilizing	0.935	D	0.513	neutral	None	None	None	None	N
S/I	0.1376	likely_benign	0.1395	benign	0.385	Stabilizing	0.38	N	0.571	neutral	None	None	None	None	N
S/K	0.6154	likely_pathogenic	0.573	pathogenic	-0.33	Destabilizing	0.149	N	0.36	neutral	None	None	None	None	N
S/L	0.0886	likely_benign	0.0886	benign	0.385	Stabilizing	0.081	N	0.479	neutral	None	None	None	None	N
S/M	0.1581	likely_benign	0.1508	benign	0.284	Stabilizing	0.824	D	0.513	neutral	None	None	None	None	N
S/N	0.1526	likely_benign	0.1553	benign	-0.61	Destabilizing	0.149	N	0.38	neutral	None	None	None	None	N
S/P	0.9212	likely_pathogenic	0.9077	pathogenic	0.156	Stabilizing	0.317	N	0.484	neutral	N	0.518980642	None	None	N
S/Q	0.4106	ambiguous	0.381	ambiguous	-0.504	Destabilizing	0.555	D	0.457	neutral	None	None	None	None	N
S/R	0.5098	ambiguous	0.4922	ambiguous	-0.541	Destabilizing	0.38	N	0.499	neutral	None	None	None	None	N
S/T	0.07	likely_benign	0.0691	benign	-0.418	Destabilizing	0.002	N	0.2	neutral	N	0.442813181	None	None	N
S/V	0.1555	likely_benign	0.1484	benign	0.156	Stabilizing	0.081	N	0.468	neutral	None	None	None	None	N
S/W	0.3373	likely_benign	0.318	benign	-0.6	Destabilizing	0.935	D	0.673	neutral	None	None	None	None	N
S/Y	0.1689	likely_benign	0.1619	benign	-0.189	Destabilizing	0.484	N	0.604	neutral	N	0.507624337	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.