TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8970	27133;27134;27135	chr2:178713226;178713225;178713224	chr2:179577953;179577952;179577951
N2AB	8653	26182;26183;26184	chr2:178713226;178713225;178713224	chr2:179577953;179577952;179577951
N2A	7726	23401;23402;23403	chr2:178713226;178713225;178713224	chr2:179577953;179577952;179577951
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: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-75
• Domain position: 45
• Structural Position: 102
• Q(SASA): 0.6804
• 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/K	rs879143084	None	0.086	N	0.154	0.068	0.0954503805726	gnomAD-4.0.0	1.59201E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88324E-05	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	0.1504	likely_benign	0.158	benign	-0.129	Destabilizing	0.003	N	0.095	neutral	None	None	None	None	N
R/C	0.123	likely_benign	0.1442	benign	-0.431	Destabilizing	0.968	D	0.235	neutral	None	None	None	None	N
R/D	0.2162	likely_benign	0.208	benign	-0.455	Destabilizing	0.001	N	0.096	neutral	None	None	None	None	N
R/E	0.1323	likely_benign	0.1409	benign	-0.44	Destabilizing	0.002	N	0.093	neutral	None	None	None	None	N
R/F	0.2925	likely_benign	0.3017	benign	-0.499	Destabilizing	0.002	N	0.186	neutral	None	None	None	None	N
R/G	0.0912	likely_benign	0.099	benign	-0.208	Destabilizing	None	N	0.091	neutral	N	0.43242475	None	None	N
R/H	0.0846	likely_benign	0.0836	benign	-0.67	Destabilizing	0.83	D	0.23	neutral	None	None	None	None	N
R/I	0.1135	likely_benign	0.1214	benign	0.034	Stabilizing	0.582	D	0.381	neutral	None	None	None	None	N
R/K	0.0751	likely_benign	0.0794	benign	-0.418	Destabilizing	0.086	N	0.154	neutral	N	0.46782819	None	None	N
R/L	0.1247	likely_benign	0.1267	benign	0.034	Stabilizing	0.223	N	0.221	neutral	None	None	None	None	N
R/M	0.1279	likely_benign	0.142	benign	-0.293	Destabilizing	0.958	D	0.248	neutral	N	0.465731746	None	None	N
R/N	0.2082	likely_benign	0.2063	benign	-0.335	Destabilizing	0.223	N	0.245	neutral	None	None	None	None	N
R/P	0.1484	likely_benign	0.1349	benign	-0.007	Destabilizing	0.002	N	0.127	neutral	None	None	None	None	N
R/Q	0.0694	likely_benign	0.0711	benign	-0.343	Destabilizing	0.223	N	0.25	neutral	None	None	None	None	N
R/S	0.1609	likely_benign	0.164	benign	-0.442	Destabilizing	0.086	N	0.235	neutral	N	0.400352404	None	None	N
R/T	0.1066	likely_benign	0.1154	benign	-0.355	Destabilizing	0.302	N	0.243	neutral	N	0.466462753	None	None	N
R/V	0.1611	likely_benign	0.1677	benign	-0.007	Destabilizing	0.365	N	0.233	neutral	None	None	None	None	N
R/W	0.1125	likely_benign	0.1198	benign	-0.734	Destabilizing	0.882	D	0.235	neutral	N	0.465731746	None	None	N
R/Y	0.2064	likely_benign	0.2193	benign	-0.38	Destabilizing	0.008	N	0.132	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.