TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6473	19642;19643;19644	chr2:178728509;178728508;178728507	chr2:179593236;179593235;179593234
N2AB	6156	18691;18692;18693	chr2:178728509;178728508;178728507	chr2:179593236;179593235;179593234
N2A	5229	15910;15911;15912	chr2:178728509;178728508;178728507	chr2:179593236;179593235;179593234
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-48
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.6671
• 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
R/I	rs747454325	0.26	0.006	N	0.171	0.322	0.494500980894	gnomAD-2.1.1	1.8E-05	None	None	None	None	N	None	2.08229E-04	0	None	0	0	None	0	None	0	0	0
R/I	rs747454325	0.26	0.006	N	0.171	0.322	0.494500980894	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.20674E-04	0	0	0	0	None	0	0	0	0	0
R/I	rs747454325	0.26	0.006	N	0.171	0.322	0.494500980894	gnomAD-4.0.0	6.21323E-06	None	None	None	None	N	None	1.33647E-04	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
R/A	0.2563	likely_benign	0.2679	benign	-0.439	Destabilizing	0.111	N	0.223	neutral	None	None	None	None	N
R/C	0.1967	likely_benign	0.1963	benign	-0.474	Destabilizing	0.968	D	0.346	neutral	None	None	None	None	N
R/D	0.4495	ambiguous	0.4484	ambiguous	0.148	Stabilizing	0.002	N	0.125	neutral	None	None	None	None	N
R/E	0.2374	likely_benign	0.2435	benign	0.236	Stabilizing	0.223	N	0.203	neutral	None	None	None	None	N
R/F	0.4588	ambiguous	0.4691	ambiguous	-0.53	Destabilizing	0.738	D	0.443	neutral	None	None	None	None	N
R/G	0.2207	likely_benign	0.2297	benign	-0.683	Destabilizing	0.086	N	0.317	neutral	N	0.504640792	None	None	N
R/H	0.0748	likely_benign	0.0749	benign	-1.026	Destabilizing	0.908	D	0.319	neutral	None	None	None	None	N
R/I	0.1993	likely_benign	0.2062	benign	0.186	Stabilizing	0.006	N	0.171	neutral	N	0.405708736	None	None	N
R/K	0.0839	likely_benign	0.0826	benign	-0.354	Destabilizing	0.302	N	0.229	neutral	N	0.435239422	None	None	N
R/L	0.1877	likely_benign	0.1861	benign	0.186	Stabilizing	0.111	N	0.273	neutral	None	None	None	None	N
R/M	0.1959	likely_benign	0.2023	benign	-0.155	Destabilizing	0.908	D	0.338	neutral	None	None	None	None	N
R/N	0.2906	likely_benign	0.2867	benign	0.071	Stabilizing	0.001	N	0.068	neutral	None	None	None	None	N
R/P	0.8547	likely_pathogenic	0.8544	pathogenic	-0.002	Destabilizing	0.738	D	0.47	neutral	None	None	None	None	N
R/Q	0.0882	likely_benign	0.0892	benign	-0.119	Destabilizing	0.582	D	0.365	neutral	None	None	None	None	N
R/S	0.2381	likely_benign	0.2626	benign	-0.595	Destabilizing	0.086	N	0.265	neutral	N	0.444168336	None	None	N
R/T	0.0995	likely_benign	0.1099	benign	-0.346	Destabilizing	0.002	N	0.12	neutral	N	0.356317278	None	None	N
R/V	0.2433	likely_benign	0.2546	benign	-0.002	Destabilizing	0.008	N	0.163	neutral	None	None	None	None	N
R/W	0.1828	likely_benign	0.1895	benign	-0.356	Destabilizing	0.991	D	0.343	neutral	None	None	None	None	N
R/Y	0.3133	likely_benign	0.3131	benign	0.004	Stabilizing	0.896	D	0.403	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.