TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4823	14692;14693;14694	chr2:178735979;178735978;178735977	chr2:179600706;179600705;179600704
N2AB	4506	13741;13742;13743	chr2:178735979;178735978;178735977	chr2:179600706;179600705;179600704
N2A	3579	10960;10961;10962	chr2:178735979;178735978;178735977	chr2:179600706;179600705;179600704
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-31
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.7986
• Predicted PPI site: I

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
V/M	None	None	0.484	N	0.329	0.119	0.398133443147	gnomAD-4.0.0	1.59138E-06	None	None	None	None	I	None	0	0	None	0	2.77423E-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
V/A	0.1179	likely_benign	0.0997	benign	-0.497	Destabilizing	0.027	N	0.33	neutral	N	0.505152573	None	None	I
V/C	0.7189	likely_pathogenic	0.6436	pathogenic	-0.716	Destabilizing	0.824	D	0.382	neutral	None	None	None	None	I
V/D	0.2086	likely_benign	0.1703	benign	-0.482	Destabilizing	0.149	N	0.463	neutral	None	None	None	None	I
V/E	0.1916	likely_benign	0.1506	benign	-0.591	Destabilizing	0.117	N	0.459	neutral	N	0.476574525	None	None	I
V/F	0.1329	likely_benign	0.1248	benign	-0.705	Destabilizing	0.555	D	0.361	neutral	None	None	None	None	I
V/G	0.1663	likely_benign	0.133	benign	-0.616	Destabilizing	0.117	N	0.455	neutral	D	0.601678815	None	None	I
V/H	0.4191	ambiguous	0.361	ambiguous	-0.14	Destabilizing	0.935	D	0.452	neutral	None	None	None	None	I
V/I	0.0767	likely_benign	0.0739	benign	-0.326	Destabilizing	0.081	N	0.331	neutral	None	None	None	None	I
V/K	0.2231	likely_benign	0.169	benign	-0.56	Destabilizing	0.149	N	0.457	neutral	None	None	None	None	I
V/L	0.1347	likely_benign	0.1177	benign	-0.326	Destabilizing	0.027	N	0.348	neutral	N	0.49697326	None	None	I
V/M	0.1093	likely_benign	0.0982	benign	-0.498	Destabilizing	0.484	N	0.329	neutral	N	0.510030713	None	None	I
V/N	0.1533	likely_benign	0.1329	benign	-0.329	Destabilizing	0.38	N	0.465	neutral	None	None	None	None	I
V/P	0.2937	likely_benign	0.2436	benign	-0.35	Destabilizing	None	N	0.193	neutral	None	None	None	None	I
V/Q	0.2214	likely_benign	0.1768	benign	-0.565	Destabilizing	0.555	D	0.456	neutral	None	None	None	None	I
V/R	0.2028	likely_benign	0.1606	benign	-0.023	Destabilizing	0.38	N	0.467	neutral	None	None	None	None	I
V/S	0.1357	likely_benign	0.1168	benign	-0.646	Destabilizing	0.081	N	0.443	neutral	None	None	None	None	I
V/T	0.1224	likely_benign	0.1028	benign	-0.658	Destabilizing	0.001	N	0.19	neutral	None	None	None	None	I
V/W	0.757	likely_pathogenic	0.6869	pathogenic	-0.781	Destabilizing	0.935	D	0.545	neutral	None	None	None	None	I
V/Y	0.4427	ambiguous	0.3918	ambiguous	-0.502	Destabilizing	0.555	D	0.359	neutral	None	None	None	None	I

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.