TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28758	86497;86498;86499	chr2:178559860;178559859;178559858	chr2:179424587;179424586;179424585
N2AB	27117	81574;81575;81576	chr2:178559860;178559859;178559858	chr2:179424587;179424586;179424585
N2A	26190	78793;78794;78795	chr2:178559860;178559859;178559858	chr2:179424587;179424586;179424585
N2B	19693	59302;59303;59304	chr2:178559860;178559859;178559858	chr2:179424587;179424586;179424585
Novex-1	19818	59677;59678;59679	chr2:178559860;178559859;178559858	chr2:179424587;179424586;179424585
Novex-2	19885	59878;59879;59880	chr2:178559860;178559859;178559858	chr2:179424587;179424586;179424585
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: Ig-144
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.558
• 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/G	None	None	0.027	N	0.342	0.194	0.173771789658	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0734	likely_benign	0.0706	benign	-0.159	Destabilizing	None	N	0.207	neutral	None	None	None	None	N
S/C	0.1047	likely_benign	0.1082	benign	-0.251	Destabilizing	0.78	D	0.375	neutral	N	0.484262733	None	None	N
S/D	0.3162	likely_benign	0.3017	benign	0.07	Stabilizing	0.081	N	0.33	neutral	None	None	None	None	N
S/E	0.4543	ambiguous	0.4443	ambiguous	-0.029	Destabilizing	0.149	N	0.317	neutral	None	None	None	None	N
S/F	0.2439	likely_benign	0.2254	benign	-0.764	Destabilizing	0.555	D	0.445	neutral	None	None	None	None	N
S/G	0.0679	likely_benign	0.0679	benign	-0.257	Destabilizing	0.027	N	0.342	neutral	N	0.435007348	None	None	N
S/H	0.3024	likely_benign	0.2886	benign	-0.66	Destabilizing	0.555	D	0.377	neutral	None	None	None	None	N
S/I	0.1358	likely_benign	0.1275	benign	-0.036	Destabilizing	0.188	N	0.461	neutral	N	0.513102773	None	None	N
S/K	0.545	ambiguous	0.5238	ambiguous	-0.463	Destabilizing	0.149	N	0.317	neutral	None	None	None	None	N
S/L	0.0988	likely_benign	0.0958	benign	-0.036	Destabilizing	0.081	N	0.403	neutral	None	None	None	None	N
S/M	0.1684	likely_benign	0.1633	benign	0.042	Stabilizing	0.555	D	0.377	neutral	None	None	None	None	N
S/N	0.0929	likely_benign	0.0884	benign	-0.147	Destabilizing	None	N	0.196	neutral	N	0.453073034	None	None	N
S/P	0.1213	likely_benign	0.1143	benign	-0.049	Destabilizing	0.555	D	0.399	neutral	None	None	None	None	N
S/Q	0.4182	ambiguous	0.4043	ambiguous	-0.386	Destabilizing	0.555	D	0.372	neutral	None	None	None	None	N
S/R	0.4805	ambiguous	0.4619	ambiguous	-0.205	Destabilizing	0.117	N	0.428	neutral	N	0.416093514	None	None	N
S/T	0.0741	likely_benign	0.0685	benign	-0.247	Destabilizing	None	N	0.211	neutral	N	0.493476862	None	None	N
S/V	0.1455	likely_benign	0.1362	benign	-0.049	Destabilizing	0.081	N	0.396	neutral	None	None	None	None	N
S/W	0.3421	ambiguous	0.3388	benign	-0.828	Destabilizing	0.935	D	0.494	neutral	None	None	None	None	N
S/Y	0.2	likely_benign	0.1926	benign	-0.528	Destabilizing	0.555	D	0.443	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.