TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7945	24058;24059;24060	chr2:178719659;178719658;178719657	chr2:179584386;179584385;179584384
N2AB	7628	23107;23108;23109	chr2:178719659;178719658;178719657	chr2:179584386;179584385;179584384
N2A	6701	20326;20327;20328	chr2:178719659;178719658;178719657	chr2:179584386;179584385;179584384
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-64
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.2092
• 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/C	rs867642789	None	0.013	N	0.372	0.346	0.37281450598	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93573E-04	None	0	0	0	0	0
S/C	rs867642789	None	0.013	N	0.372	0.346	0.37281450598	gnomAD-4.0.0	2.30631E-05	None	None	None	None	N	None	0	0	None	0	4.36533E-04	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	0.0911	likely_benign	0.0979	benign	-0.762	Destabilizing	0.139	N	0.325	neutral	N	0.495229117	None	None	N
S/C	0.1105	likely_benign	0.1252	benign	-0.549	Destabilizing	0.013	N	0.372	neutral	N	0.486634744	None	None	N
S/D	0.6357	likely_pathogenic	0.6827	pathogenic	-1.451	Destabilizing	0.704	D	0.443	neutral	None	None	None	None	N
S/E	0.6445	likely_pathogenic	0.6939	pathogenic	-1.235	Destabilizing	0.704	D	0.445	neutral	None	None	None	None	N
S/F	0.1529	likely_benign	0.1793	benign	-0.594	Destabilizing	0.927	D	0.603	neutral	N	0.497395165	None	None	N
S/G	0.122	likely_benign	0.1227	benign	-1.181	Destabilizing	0.495	N	0.377	neutral	None	None	None	None	N
S/H	0.3341	likely_benign	0.3701	ambiguous	-1.559	Destabilizing	0.981	D	0.57	neutral	None	None	None	None	N
S/I	0.1417	likely_benign	0.1558	benign	0.311	Stabilizing	0.543	D	0.561	neutral	None	None	None	None	N
S/K	0.6943	likely_pathogenic	0.7414	pathogenic	-0.174	Destabilizing	0.543	D	0.429	neutral	None	None	None	None	N
S/L	0.0922	likely_benign	0.1037	benign	0.311	Stabilizing	0.329	N	0.479	neutral	None	None	None	None	N
S/M	0.1828	likely_benign	0.2098	benign	0.168	Stabilizing	0.944	D	0.563	neutral	None	None	None	None	N
S/N	0.1793	likely_benign	0.204	benign	-0.968	Destabilizing	0.704	D	0.457	neutral	None	None	None	None	N
S/P	0.9289	likely_pathogenic	0.9323	pathogenic	-0.011	Destabilizing	0.927	D	0.554	neutral	D	0.522096012	None	None	N
S/Q	0.5177	ambiguous	0.5692	pathogenic	-0.651	Destabilizing	0.944	D	0.52	neutral	None	None	None	None	N
S/R	0.5604	ambiguous	0.6023	pathogenic	-0.649	Destabilizing	0.031	N	0.388	neutral	None	None	None	None	N
S/T	0.0764	likely_benign	0.0853	benign	-0.585	Destabilizing	0.01	N	0.221	neutral	N	0.443858905	None	None	N
S/V	0.1542	likely_benign	0.1738	benign	-0.011	Destabilizing	0.031	N	0.499	neutral	None	None	None	None	N
S/W	0.3435	ambiguous	0.3672	ambiguous	-0.909	Destabilizing	0.995	D	0.701	prob.neutral	None	None	None	None	N
S/Y	0.1564	likely_benign	0.1776	benign	-0.42	Destabilizing	0.975	D	0.595	neutral	N	0.497902144	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.