TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20238	60937;60938;60939	chr2:178591013;178591012;178591011	chr2:179455740;179455739;179455738
N2AB	18597	56014;56015;56016	chr2:178591013;178591012;178591011	chr2:179455740;179455739;179455738
N2A	17670	53233;53234;53235	chr2:178591013;178591012;178591011	chr2:179455740;179455739;179455738
N2B	11173	33742;33743;33744	chr2:178591013;178591012;178591011	chr2:179455740;179455739;179455738
Novex-1	11298	34117;34118;34119	chr2:178591013;178591012;178591011	chr2:179455740;179455739;179455738
Novex-2	11365	34318;34319;34320	chr2:178591013;178591012;178591011	chr2:179455740;179455739;179455738
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-34
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.4247
• 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	None	None	0.121	N	0.274	0.14	0.310147130316	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.2449	likely_benign	0.2454	benign	-0.028	Destabilizing	0.983	D	0.475	neutral	None	None	None	None	N
K/C	0.7116	likely_pathogenic	0.7087	pathogenic	-0.209	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
K/D	0.4427	ambiguous	0.4428	ambiguous	0.014	Stabilizing	0.995	D	0.421	neutral	None	None	None	None	N
K/E	0.1188	likely_benign	0.1336	benign	0.038	Stabilizing	0.956	D	0.533	neutral	N	0.366213693	None	None	N
K/F	0.7962	likely_pathogenic	0.7916	pathogenic	-0.12	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	N
K/G	0.4376	ambiguous	0.4457	ambiguous	-0.262	Destabilizing	0.992	D	0.449	neutral	None	None	None	None	N
K/H	0.332	likely_benign	0.3309	benign	-0.525	Destabilizing	0.999	D	0.425	neutral	None	None	None	None	N
K/I	0.352	ambiguous	0.3599	ambiguous	0.518	Stabilizing	0.999	D	0.603	neutral	None	None	None	None	N
K/L	0.3522	ambiguous	0.3538	ambiguous	0.518	Stabilizing	0.983	D	0.449	neutral	None	None	None	None	N
K/M	0.2101	likely_benign	0.2168	benign	0.251	Stabilizing	1.0	D	0.425	neutral	N	0.473343945	None	None	N
K/N	0.3367	likely_benign	0.3514	ambiguous	0.149	Stabilizing	0.997	D	0.513	neutral	N	0.471207717	None	None	N
K/P	0.351	ambiguous	0.3333	benign	0.365	Stabilizing	0.999	D	0.44	neutral	None	None	None	None	N
K/Q	0.1269	likely_benign	0.1278	benign	-0.002	Destabilizing	0.798	D	0.284	neutral	N	0.427032865	None	None	N
K/R	0.0927	likely_benign	0.0977	benign	-0.111	Destabilizing	0.121	N	0.274	neutral	N	0.493199142	None	None	N
K/S	0.3279	likely_benign	0.3298	benign	-0.338	Destabilizing	0.983	D	0.539	neutral	None	None	None	None	N
K/T	0.1547	likely_benign	0.1588	benign	-0.155	Destabilizing	0.997	D	0.411	neutral	N	0.469514206	None	None	N
K/V	0.3025	likely_benign	0.3026	benign	0.365	Stabilizing	0.998	D	0.503	neutral	None	None	None	None	N
K/W	0.7863	likely_pathogenic	0.7781	pathogenic	-0.121	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
K/Y	0.6202	likely_pathogenic	0.6158	pathogenic	0.215	Stabilizing	0.999	D	0.538	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.