TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8525	25798;25799;25800	chr2:178717161;178717160;178717159	chr2:179581888;179581887;179581886
N2AB	8208	24847;24848;24849	chr2:178717161;178717160;178717159	chr2:179581888;179581887;179581886
N2A	7281	22066;22067;22068	chr2:178717161;178717160;178717159	chr2:179581888;179581887;179581886
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-70
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.4596
• 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
Q/L	None	None	None	N	0.239	0.301	0.270447802918	gnomAD-4.0.0	2.05295E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69876E-06	0	0
Q/P	rs2077609752	None	0.224	N	0.461	0.29	0.233785782151	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Q/P	rs2077609752	None	0.224	N	0.461	0.29	0.233785782151	gnomAD-4.0.0	6.57013E-06	None	None	None	None	N	None	2.41103E-05	0	None	0	0	None	0	0	0	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
Q/A	0.2091	likely_benign	0.2036	benign	-0.488	Destabilizing	0.024	N	0.271	neutral	None	None	None	None	N
Q/C	0.5726	likely_pathogenic	0.5761	pathogenic	0.058	Stabilizing	0.803	D	0.526	neutral	None	None	None	None	N
Q/D	0.3366	likely_benign	0.3314	benign	-0.863	Destabilizing	0.037	N	0.31	neutral	None	None	None	None	N
Q/E	0.0879	likely_benign	0.087	benign	-0.816	Destabilizing	None	N	0.121	neutral	N	0.40807425	None	None	N
Q/F	0.4713	ambiguous	0.4672	ambiguous	-0.602	Destabilizing	0.259	N	0.599	neutral	None	None	None	None	N
Q/G	0.3006	likely_benign	0.2954	benign	-0.773	Destabilizing	0.001	N	0.229	neutral	None	None	None	None	N
Q/H	0.1502	likely_benign	0.1518	benign	-0.96	Destabilizing	0.572	D	0.407	neutral	N	0.472645804	None	None	N
Q/I	0.1988	likely_benign	0.1959	benign	0.209	Stabilizing	0.049	N	0.438	neutral	None	None	None	None	N
Q/K	0.0916	likely_benign	0.0913	benign	-0.137	Destabilizing	None	N	0.123	neutral	N	0.421483478	None	None	N
Q/L	0.0832	likely_benign	0.0808	benign	0.209	Stabilizing	None	N	0.239	neutral	N	0.419774111	None	None	N
Q/M	0.2579	likely_benign	0.2449	benign	0.841	Stabilizing	0.467	N	0.421	neutral	None	None	None	None	N
Q/N	0.2233	likely_benign	0.2135	benign	-0.664	Destabilizing	0.072	N	0.358	neutral	None	None	None	None	N
Q/P	0.1826	likely_benign	0.1833	benign	0.007	Stabilizing	0.224	N	0.461	neutral	N	0.498002821	None	None	N
Q/R	0.1002	likely_benign	0.0988	benign	-0.07	Destabilizing	0.001	N	0.123	neutral	N	0.43497285	None	None	N
Q/S	0.2304	likely_benign	0.2189	benign	-0.68	Destabilizing	0.053	N	0.253	neutral	None	None	None	None	N
Q/T	0.1652	likely_benign	0.1605	benign	-0.454	Destabilizing	0.01	N	0.345	neutral	None	None	None	None	N
Q/V	0.1529	likely_benign	0.1471	benign	0.007	Stabilizing	None	N	0.238	neutral	None	None	None	None	N
Q/W	0.3629	ambiguous	0.3662	ambiguous	-0.539	Destabilizing	0.987	D	0.523	neutral	None	None	None	None	N
Q/Y	0.3196	likely_benign	0.3138	benign	-0.235	Destabilizing	0.414	N	0.517	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.