TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18018	54277;54278;54279	chr2:178605125;178605124;178605123	chr2:179469852;179469851;179469850
N2AB	16377	49354;49355;49356	chr2:178605125;178605124;178605123	chr2:179469852;179469851;179469850
N2A	15450	46573;46574;46575	chr2:178605125;178605124;178605123	chr2:179469852;179469851;179469850
N2B	8953	27082;27083;27084	chr2:178605125;178605124;178605123	chr2:179469852;179469851;179469850
Novex-1	9078	27457;27458;27459	chr2:178605125;178605124;178605123	chr2:179469852;179469851;179469850
Novex-2	9145	27658;27659;27660	chr2:178605125;178605124;178605123	chr2:179469852;179469851;179469850
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-114
• Domain position: 51
• Structural Position: 120
• Q(SASA): 0.3213
• 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	rs2054476187	None	0.117	N	0.421	0.242	0.269111216191	gnomAD-4.0.0	1.27475E-05	None	None	None	None	N	None	0	0	None	0	2.22692E-04	None	0	0	0	0	0
K/M	rs368425364	0.319	0.484	N	0.524	0.192	None	gnomAD-2.1.1	8.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	1.19971E-04	1.49576E-04	2.81928E-04
K/M	rs368425364	0.319	0.484	N	0.524	0.192	None	gnomAD-3.1.2	7.9E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	9.41E-05	0	1.47184E-04	0	0
K/M	rs368425364	0.319	0.484	N	0.524	0.192	None	gnomAD-4.0.0	8.92918E-05	None	None	None	None	N	None	1.33643E-05	0	None	0	0	None	1.40616E-04	0	1.06849E-04	0	1.28189E-04

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	0.2459	likely_benign	0.2853	benign	-0.104	Destabilizing	0.035	N	0.451	neutral	None	None	None	None	N
K/C	0.625	likely_pathogenic	0.663	pathogenic	-0.249	Destabilizing	0.824	D	0.572	neutral	None	None	None	None	N
K/D	0.5769	likely_pathogenic	0.6303	pathogenic	0.196	Stabilizing	0.149	N	0.462	neutral	None	None	None	None	N
K/E	0.1424	likely_benign	0.1591	benign	0.25	Stabilizing	0.117	N	0.421	neutral	N	0.420350114	None	None	N
K/F	0.7343	likely_pathogenic	0.7803	pathogenic	-0.079	Destabilizing	0.555	D	0.587	neutral	None	None	None	None	N
K/G	0.3939	ambiguous	0.4457	ambiguous	-0.386	Destabilizing	0.149	N	0.523	neutral	None	None	None	None	N
K/H	0.2798	likely_benign	0.3051	benign	-0.723	Destabilizing	0.791	D	0.523	neutral	None	None	None	None	N
K/I	0.3226	likely_benign	0.3687	ambiguous	0.578	Stabilizing	0.235	N	0.569	neutral	None	None	None	None	N
K/L	0.3159	likely_benign	0.3608	ambiguous	0.578	Stabilizing	0.081	N	0.523	neutral	None	None	None	None	N
K/M	0.2102	likely_benign	0.2381	benign	0.317	Stabilizing	0.484	N	0.524	neutral	N	0.50379543	None	None	N
K/N	0.4011	ambiguous	0.4409	ambiguous	0.076	Stabilizing	0.117	N	0.461	neutral	N	0.391702075	None	None	N
K/P	0.7899	likely_pathogenic	0.8012	pathogenic	0.382	Stabilizing	0.555	D	0.524	neutral	None	None	None	None	N
K/Q	0.1192	likely_benign	0.1248	benign	-0.029	Destabilizing	0.484	N	0.543	neutral	N	0.44393905	None	None	N
K/R	0.0835	likely_benign	0.0858	benign	-0.205	Destabilizing	0.117	N	0.461	neutral	N	0.444112408	None	None	N
K/S	0.2927	likely_benign	0.3314	benign	-0.479	Destabilizing	0.007	N	0.231	neutral	None	None	None	None	N
K/T	0.0989	likely_benign	0.1136	benign	-0.244	Destabilizing	None	N	0.326	neutral	N	0.372462954	None	None	N
K/V	0.2452	likely_benign	0.2862	benign	0.382	Stabilizing	0.081	N	0.53	neutral	None	None	None	None	N
K/W	0.7057	likely_pathogenic	0.7413	pathogenic	-0.045	Destabilizing	0.935	D	0.6	neutral	None	None	None	None	N
K/Y	0.5787	likely_pathogenic	0.6275	pathogenic	0.289	Stabilizing	0.555	D	0.583	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.