TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16036	48331;48332;48333	chr2:178616783;178616782;178616781	chr2:179481510;179481509;179481508
N2AB	14395	43408;43409;43410	chr2:178616783;178616782;178616781	chr2:179481510;179481509;179481508
N2A	13468	40627;40628;40629	chr2:178616783;178616782;178616781	chr2:179481510;179481509;179481508
N2B	6971	21136;21137;21138	chr2:178616783;178616782;178616781	chr2:179481510;179481509;179481508
Novex-1	7096	21511;21512;21513	chr2:178616783;178616782;178616781	chr2:179481510;179481509;179481508
Novex-2	7163	21712;21713;21714	chr2:178616783;178616782;178616781	chr2:179481510;179481509;179481508
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-109
• Domain position: 69
• Structural Position: 157
• Q(SASA): 0.3403
• 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
K/Q	rs886055271	None	None	N	0.246	0.14	0.203808441222	gnomAD-4.0.0	4.79216E-06	None	None	None	None	N	None	0	0	None	0	2.5236E-05	None	0	0	8.99865E-07	0	8.29105E-05

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
K/A	0.3378	likely_benign	0.3502	ambiguous	-0.623	Destabilizing	0.007	N	0.35	neutral	None	None	None	None	N
K/C	0.5082	ambiguous	0.5405	ambiguous	-0.87	Destabilizing	0.676	D	0.524	neutral	None	None	None	None	N
K/D	0.6154	likely_pathogenic	0.6505	pathogenic	-0.371	Destabilizing	0.016	N	0.403	neutral	None	None	None	None	N
K/E	0.1709	likely_benign	0.1967	benign	-0.295	Destabilizing	None	N	0.235	neutral	N	0.460057057	None	None	N
K/F	0.6291	likely_pathogenic	0.6179	pathogenic	-0.663	Destabilizing	0.356	N	0.575	neutral	None	None	None	None	N
K/G	0.5671	likely_pathogenic	0.5834	pathogenic	-0.931	Destabilizing	0.016	N	0.463	neutral	None	None	None	None	N
K/H	0.1774	likely_benign	0.1879	benign	-1.36	Destabilizing	None	N	0.342	neutral	None	None	None	None	N
K/I	0.1924	likely_benign	0.2065	benign	0.153	Stabilizing	0.029	N	0.585	neutral	N	0.482922463	None	None	N
K/L	0.2322	likely_benign	0.2326	benign	0.153	Stabilizing	0.016	N	0.462	neutral	None	None	None	None	N
K/M	0.1405	likely_benign	0.1559	benign	0.161	Stabilizing	0.356	N	0.512	neutral	None	None	None	None	N
K/N	0.2994	likely_benign	0.3274	benign	-0.449	Destabilizing	None	N	0.219	neutral	N	0.507088738	None	None	N
K/P	0.9725	likely_pathogenic	0.9695	pathogenic	-0.077	Destabilizing	0.136	N	0.493	neutral	None	None	None	None	N
K/Q	0.1005	likely_benign	0.1132	benign	-0.688	Destabilizing	None	N	0.246	neutral	N	0.387216009	None	None	N
K/R	0.0849	likely_benign	0.0918	benign	-0.462	Destabilizing	0.012	N	0.387	neutral	N	0.477458347	None	None	N
K/S	0.2981	likely_benign	0.308	benign	-1.129	Destabilizing	0.007	N	0.283	neutral	None	None	None	None	N
K/T	0.0757	likely_benign	0.0823	benign	-0.863	Destabilizing	None	N	0.295	neutral	N	0.385775787	None	None	N
K/V	0.2088	likely_benign	0.2318	benign	-0.077	Destabilizing	0.016	N	0.459	neutral	None	None	None	None	N
K/W	0.6961	likely_pathogenic	0.6827	pathogenic	-0.509	Destabilizing	0.864	D	0.536	neutral	None	None	None	None	N
K/Y	0.4726	ambiguous	0.4726	ambiguous	-0.141	Destabilizing	0.072	N	0.605	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.