TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20228	60907;60908;60909	chr2:178591043;178591042;178591041	chr2:179455770;179455769;179455768
N2AB	18587	55984;55985;55986	chr2:178591043;178591042;178591041	chr2:179455770;179455769;179455768
N2A	17660	53203;53204;53205	chr2:178591043;178591042;178591041	chr2:179455770;179455769;179455768
N2B	11163	33712;33713;33714	chr2:178591043;178591042;178591041	chr2:179455770;179455769;179455768
Novex-1	11288	34087;34088;34089	chr2:178591043;178591042;178591041	chr2:179455770;179455769;179455768
Novex-2	11355	34288;34289;34290	chr2:178591043;178591042;178591041	chr2:179455770;179455769;179455768
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: 58
• Structural Position: 88
• Q(SASA): 0.4459
• 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	0.27	N	0.281	0.064	0.238705975628	gnomAD-4.0.0	1.592E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85984E-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	0.2435	likely_benign	0.3166	benign	-0.056	Destabilizing	0.004	N	0.192	neutral	None	None	None	None	N
K/C	0.5662	likely_pathogenic	0.5969	pathogenic	-0.469	Destabilizing	0.981	D	0.425	neutral	None	None	None	None	N
K/D	0.4421	ambiguous	0.579	pathogenic	0.285	Stabilizing	0.495	N	0.364	neutral	None	None	None	None	N
K/E	0.1679	likely_benign	0.2458	benign	0.316	Stabilizing	0.27	N	0.209	neutral	N	0.438977868	None	None	N
K/F	0.6988	likely_pathogenic	0.7654	pathogenic	-0.272	Destabilizing	0.944	D	0.506	neutral	None	None	None	None	N
K/G	0.3204	likely_benign	0.4154	ambiguous	-0.244	Destabilizing	0.003	N	0.249	neutral	None	None	None	None	N
K/H	0.2534	likely_benign	0.2946	benign	-0.357	Destabilizing	0.007	N	0.237	neutral	None	None	None	None	N
K/I	0.3428	ambiguous	0.4093	ambiguous	0.362	Stabilizing	0.828	D	0.539	neutral	None	None	None	None	N
K/L	0.3191	likely_benign	0.3887	ambiguous	0.362	Stabilizing	0.495	N	0.368	neutral	None	None	None	None	N
K/M	0.2182	likely_benign	0.282	benign	-0.042	Destabilizing	0.927	D	0.413	neutral	N	0.477586983	None	None	N
K/N	0.3319	likely_benign	0.4464	ambiguous	0.027	Stabilizing	0.425	N	0.247	neutral	N	0.458779924	None	None	N
K/P	0.6522	likely_pathogenic	0.7567	pathogenic	0.249	Stabilizing	0.828	D	0.449	neutral	None	None	None	None	N
K/Q	0.1203	likely_benign	0.1425	benign	-0.033	Destabilizing	0.023	N	0.123	neutral	N	0.463126951	None	None	N
K/R	0.0785	likely_benign	0.0821	benign	-0.014	Destabilizing	0.27	N	0.281	neutral	N	0.404484079	None	None	N
K/S	0.2967	likely_benign	0.3962	ambiguous	-0.474	Destabilizing	0.013	N	0.079	neutral	None	None	None	None	N
K/T	0.1426	likely_benign	0.196	benign	-0.286	Destabilizing	0.27	N	0.339	neutral	N	0.440439306	None	None	N
K/V	0.2761	likely_benign	0.3349	benign	0.249	Stabilizing	0.495	N	0.4	neutral	None	None	None	None	N
K/W	0.7102	likely_pathogenic	0.7668	pathogenic	-0.327	Destabilizing	0.995	D	0.431	neutral	None	None	None	None	N
K/Y	0.5546	ambiguous	0.6259	pathogenic	0.037	Stabilizing	0.704	D	0.551	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.