TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17906	53941;53942;53943	chr2:178605579;178605578;178605577	chr2:179470306;179470305;179470304
N2AB	16265	49018;49019;49020	chr2:178605579;178605578;178605577	chr2:179470306;179470305;179470304
N2A	15338	46237;46238;46239	chr2:178605579;178605578;178605577	chr2:179470306;179470305;179470304
N2B	8841	26746;26747;26748	chr2:178605579;178605578;178605577	chr2:179470306;179470305;179470304
Novex-1	8966	27121;27122;27123	chr2:178605579;178605578;178605577	chr2:179470306;179470305;179470304
Novex-2	9033	27322;27323;27324	chr2:178605579;178605578;178605577	chr2:179470306;179470305;179470304
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: Fn3-18
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.3421
• 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/R	rs727503606	-0.178	None	N	0.139	0.064	None	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/R	rs727503606	-0.178	None	N	0.139	0.064	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.95E-05	0	0
K/R	rs727503606	-0.178	None	N	0.139	0.064	None	gnomAD-4.0.0	8.68364E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.18759E-05	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
K/A	0.2111	likely_benign	0.1813	benign	-0.154	Destabilizing	None	N	0.182	neutral	None	None	None	None	N
K/C	0.4493	ambiguous	0.4218	ambiguous	-0.14	Destabilizing	0.864	D	0.367	neutral	None	None	None	None	N
K/D	0.4458	ambiguous	0.4418	ambiguous	-0.055	Destabilizing	0.016	N	0.361	neutral	None	None	None	None	N
K/E	0.1596	likely_benign	0.1608	benign	-0.01	Destabilizing	None	N	0.143	neutral	N	0.404939865	None	None	N
K/F	0.5809	likely_pathogenic	0.5567	ambiguous	-0.072	Destabilizing	0.356	N	0.403	neutral	None	None	None	None	N
K/G	0.3278	likely_benign	0.2979	benign	-0.441	Destabilizing	0.016	N	0.301	neutral	None	None	None	None	N
K/H	0.1946	likely_benign	0.1954	benign	-0.836	Destabilizing	0.214	N	0.347	neutral	None	None	None	None	N
K/I	0.2757	likely_benign	0.2399	benign	0.553	Stabilizing	0.171	N	0.438	neutral	N	0.465991111	None	None	N
K/L	0.2109	likely_benign	0.1923	benign	0.553	Stabilizing	0.031	N	0.293	neutral	None	None	None	None	N
K/M	0.1657	likely_benign	0.1521	benign	0.371	Stabilizing	0.356	N	0.34	neutral	None	None	None	None	N
K/N	0.2955	likely_benign	0.2687	benign	0.012	Stabilizing	0.055	N	0.219	neutral	N	0.417581089	None	None	N
K/P	0.9445	likely_pathogenic	0.9391	pathogenic	0.347	Stabilizing	0.136	N	0.321	neutral	None	None	None	None	N
K/Q	0.09	likely_benign	0.0925	benign	-0.121	Destabilizing	None	N	0.079	neutral	N	0.407230809	None	None	N
K/R	0.0898	likely_benign	0.0971	benign	-0.386	Destabilizing	None	N	0.139	neutral	N	0.430473028	None	None	N
K/S	0.2484	likely_benign	0.2216	benign	-0.483	Destabilizing	None	N	0.131	neutral	None	None	None	None	N
K/T	0.1326	likely_benign	0.1233	benign	-0.271	Destabilizing	0.012	N	0.357	neutral	N	0.393050791	None	None	N
K/V	0.2256	likely_benign	0.2007	benign	0.347	Stabilizing	0.038	N	0.341	neutral	None	None	None	None	N
K/W	0.704	likely_pathogenic	0.7002	pathogenic	-0.04	Destabilizing	0.864	D	0.375	neutral	None	None	None	None	N
K/Y	0.4783	ambiguous	0.4689	ambiguous	0.257	Stabilizing	0.356	N	0.399	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.