TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5905	17938;17939;17940	chr2:178730952;178730951;178730950	chr2:179595679;179595678;179595677
N2AB	5588	16987;16988;16989	chr2:178730952;178730951;178730950	chr2:179595679;179595678;179595677
N2A	4661	14206;14207;14208	chr2:178730952;178730951;178730950	chr2:179595679;179595678;179595677
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-42
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.3795
• 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/N	rs756323124	-0.306	0.722	N	0.467	0.18	0.233150807113	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.97E-06	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	0.0976	benign	-0.589	Destabilizing	0.415	N	0.457	neutral	None	None	None	None	N
S/C	0.1407	likely_benign	0.1432	benign	-0.443	Destabilizing	0.995	D	0.643	neutral	D	0.524386963	None	None	N
S/D	0.4289	ambiguous	0.4488	ambiguous	-0.195	Destabilizing	0.775	D	0.441	neutral	None	None	None	None	N
S/E	0.4763	ambiguous	0.5038	ambiguous	-0.193	Destabilizing	0.775	D	0.438	neutral	None	None	None	None	N
S/F	0.1473	likely_benign	0.1655	benign	-0.716	Destabilizing	0.961	D	0.699	prob.neutral	None	None	None	None	N
S/G	0.1327	likely_benign	0.1318	benign	-0.847	Destabilizing	0.008	N	0.228	neutral	N	0.505522239	None	None	N
S/H	0.2878	likely_benign	0.2757	benign	-1.311	Destabilizing	0.996	D	0.633	neutral	None	None	None	None	N
S/I	0.1256	likely_benign	0.1314	benign	-0.012	Destabilizing	0.901	D	0.687	prob.neutral	N	0.505775729	None	None	N
S/K	0.5604	ambiguous	0.5596	ambiguous	-0.749	Destabilizing	0.775	D	0.432	neutral	None	None	None	None	N
S/L	0.1027	likely_benign	0.1101	benign	-0.012	Destabilizing	0.633	D	0.577	neutral	None	None	None	None	N
S/M	0.2208	likely_benign	0.2212	benign	0.107	Stabilizing	0.989	D	0.632	neutral	None	None	None	None	N
S/N	0.1492	likely_benign	0.1457	benign	-0.684	Destabilizing	0.722	D	0.467	neutral	N	0.491190193	None	None	N
S/P	0.8076	likely_pathogenic	0.8678	pathogenic	-0.169	Destabilizing	0.961	D	0.655	neutral	None	None	None	None	N
S/Q	0.4323	ambiguous	0.4222	ambiguous	-0.773	Destabilizing	0.961	D	0.499	neutral	None	None	None	None	N
S/R	0.4003	ambiguous	0.3928	ambiguous	-0.666	Destabilizing	0.901	D	0.649	neutral	N	0.513396348	None	None	N
S/T	0.0749	likely_benign	0.0773	benign	-0.658	Destabilizing	0.008	N	0.315	neutral	N	0.500405621	None	None	N
S/V	0.1418	likely_benign	0.1468	benign	-0.169	Destabilizing	0.858	D	0.611	neutral	None	None	None	None	N
S/W	0.3228	likely_benign	0.36	ambiguous	-0.744	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	N
S/Y	0.1664	likely_benign	0.1863	benign	-0.47	Destabilizing	0.987	D	0.698	prob.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.