TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15713	47362;47363;47364	chr2:178618321;178618320;178618319	chr2:179483048;179483047;179483046
N2AB	14072	42439;42440;42441	chr2:178618321;178618320;178618319	chr2:179483048;179483047;179483046
N2A	13145	39658;39659;39660	chr2:178618321;178618320;178618319	chr2:179483048;179483047;179483046
N2B	6648	20167;20168;20169	chr2:178618321;178618320;178618319	chr2:179483048;179483047;179483046
Novex-1	6773	20542;20543;20544	chr2:178618321;178618320;178618319	chr2:179483048;179483047;179483046
Novex-2	6840	20743;20744;20745	chr2:178618321;178618320;178618319	chr2:179483048;179483047;179483046
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-1
• Domain position: 57
• Structural Position: 88
• Q(SASA): 0.4006
• 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/R	rs1576516161	None	0.968	N	0.59	0.295	0.229924730088	gnomAD-4.0.0	1.59341E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86243E-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
S/A	0.0941	likely_benign	0.0965	benign	-0.654	Destabilizing	0.825	D	0.398	neutral	None	None	None	None	N
S/C	0.1331	likely_benign	0.1441	benign	-0.458	Destabilizing	0.999	D	0.591	neutral	N	0.50983174	None	None	N
S/D	0.2351	likely_benign	0.2495	benign	0.001	Stabilizing	0.851	D	0.415	neutral	None	None	None	None	N
S/E	0.3543	ambiguous	0.3443	ambiguous	0.02	Stabilizing	0.919	D	0.455	neutral	None	None	None	None	N
S/F	0.2415	likely_benign	0.2487	benign	-0.933	Destabilizing	0.996	D	0.629	neutral	None	None	None	None	N
S/G	0.0708	likely_benign	0.0843	benign	-0.883	Destabilizing	0.026	N	0.154	neutral	N	0.477540559	None	None	N
S/H	0.2661	likely_benign	0.2905	benign	-1.085	Destabilizing	0.997	D	0.605	neutral	None	None	None	None	N
S/I	0.1549	likely_benign	0.1899	benign	-0.146	Destabilizing	0.984	D	0.621	neutral	N	0.482029827	None	None	N
S/K	0.4875	ambiguous	0.4573	ambiguous	-0.457	Destabilizing	0.919	D	0.471	neutral	None	None	None	None	N
S/L	0.1465	likely_benign	0.1653	benign	-0.146	Destabilizing	0.988	D	0.516	neutral	None	None	None	None	N
S/M	0.1946	likely_benign	0.2177	benign	-0.226	Destabilizing	0.999	D	0.594	neutral	None	None	None	None	N
S/N	0.0758	likely_benign	0.0898	benign	-0.478	Destabilizing	0.026	N	0.231	neutral	N	0.482863495	None	None	N
S/P	0.579	likely_pathogenic	0.65	pathogenic	-0.283	Destabilizing	0.996	D	0.591	neutral	None	None	None	None	N
S/Q	0.3624	ambiguous	0.3789	ambiguous	-0.513	Destabilizing	0.988	D	0.54	neutral	None	None	None	None	N
S/R	0.4525	ambiguous	0.4482	ambiguous	-0.33	Destabilizing	0.968	D	0.59	neutral	N	0.462367205	None	None	N
S/T	0.0795	likely_benign	0.0856	benign	-0.49	Destabilizing	0.896	D	0.413	neutral	N	0.426479262	None	None	N
S/V	0.167	likely_benign	0.1933	benign	-0.283	Destabilizing	0.988	D	0.563	neutral	None	None	None	None	N
S/W	0.4243	ambiguous	0.4408	ambiguous	-0.998	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
S/Y	0.2092	likely_benign	0.2049	benign	-0.679	Destabilizing	0.996	D	0.633	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.