TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35442	106549;106550;106551	chr2:178530291;178530290;178530289	chr2:179395018;179395017;179395016
N2AB	33801	101626;101627;101628	chr2:178530291;178530290;178530289	chr2:179395018;179395017;179395016
N2A	32874	98845;98846;98847	chr2:178530291;178530290;178530289	chr2:179395018;179395017;179395016
N2B	26377	79354;79355;79356	chr2:178530291;178530290;178530289	chr2:179395018;179395017;179395016
Novex-1	26502	79729;79730;79731	chr2:178530291;178530290;178530289	chr2:179395018;179395017;179395016
Novex-2	26569	79930;79931;79932	chr2:178530291;178530290;178530289	chr2:179395018;179395017;179395016
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: Ig-166
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.4257
• 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/E	None	None	0.001	N	0.202	0.171	0.134241683229	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
K/R	rs1688520726	None	0.192	N	0.428	0.087	0.223847106136	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	0.4101	ambiguous	0.3969	ambiguous	-0.685	Destabilizing	0.115	N	0.445	neutral	None	None	None	None	N
K/C	0.8572	likely_pathogenic	0.8505	pathogenic	-0.794	Destabilizing	0.981	D	0.575	neutral	None	None	None	None	N
K/D	0.6517	likely_pathogenic	0.6333	pathogenic	-0.014	Destabilizing	0.239	N	0.485	neutral	None	None	None	None	N
K/E	0.1951	likely_benign	0.1785	benign	0.109	Stabilizing	0.001	N	0.202	neutral	N	0.464236964	None	None	N
K/F	0.7579	likely_pathogenic	0.7573	pathogenic	-0.365	Destabilizing	0.688	D	0.585	neutral	None	None	None	None	N
K/G	0.6183	likely_pathogenic	0.6109	pathogenic	-1.055	Destabilizing	0.386	N	0.541	neutral	None	None	None	None	N
K/H	0.3904	ambiguous	0.3711	ambiguous	-1.339	Destabilizing	0.002	N	0.259	neutral	None	None	None	None	N
K/I	0.3168	likely_benign	0.3026	benign	0.277	Stabilizing	0.525	D	0.59	neutral	None	None	None	None	N
K/L	0.3671	ambiguous	0.3587	ambiguous	0.277	Stabilizing	0.239	N	0.556	neutral	None	None	None	None	N
K/M	0.227	likely_benign	0.2216	benign	0.125	Stabilizing	0.771	D	0.597	neutral	D	0.529155234	None	None	N
K/N	0.3991	ambiguous	0.3803	ambiguous	-0.499	Destabilizing	0.192	N	0.461	neutral	N	0.491404923	None	None	N
K/P	0.9121	likely_pathogenic	0.9162	pathogenic	-0.014	Destabilizing	0.817	D	0.59	neutral	None	None	None	None	N
K/Q	0.1591	likely_benign	0.1488	benign	-0.579	Destabilizing	0.006	N	0.315	neutral	N	0.469162781	None	None	N
K/R	0.1087	likely_benign	0.1051	benign	-0.586	Destabilizing	0.192	N	0.428	neutral	N	0.429913747	None	None	N
K/S	0.4506	ambiguous	0.4397	ambiguous	-1.248	Destabilizing	0.115	N	0.471	neutral	None	None	None	None	N
K/T	0.1685	likely_benign	0.1582	benign	-0.912	Destabilizing	0.001	N	0.275	neutral	N	0.481686574	None	None	N
K/V	0.3475	ambiguous	0.332	benign	-0.014	Destabilizing	0.239	N	0.539	neutral	None	None	None	None	N
K/W	0.8449	likely_pathogenic	0.8415	pathogenic	-0.196	Destabilizing	0.981	D	0.594	neutral	None	None	None	None	N
K/Y	0.6614	likely_pathogenic	0.6536	pathogenic	0.106	Stabilizing	0.525	D	0.601	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.