TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6909	20950;20951;20952	chr2:178725479;178725478;178725477	chr2:179590206;179590205;179590204
N2AB	6592	19999;20000;20001	chr2:178725479;178725478;178725477	chr2:179590206;179590205;179590204
N2A	5665	17218;17219;17220	chr2:178725479;178725478;178725477	chr2:179590206;179590205;179590204
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-53
• Domain position: 56
• Structural Position: 135
• Q(SASA): 0.2119
• 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
V/D	rs1316718244	None	0.193	D	0.611	0.282	0.716185225888	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/D	rs1316718244	None	0.193	D	0.611	0.282	0.716185225888	gnomAD-4.0.0	6.57255E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4705E-05	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
V/A	0.1523	likely_benign	0.1532	benign	-1.56	Destabilizing	0.09	N	0.46	neutral	N	0.482210063	None	None	N
V/C	0.6373	likely_pathogenic	0.6168	pathogenic	-1.175	Destabilizing	0.981	D	0.511	neutral	None	None	None	None	N
V/D	0.3046	likely_benign	0.3016	benign	-1.425	Destabilizing	0.193	N	0.611	neutral	D	0.528208298	None	None	N
V/E	0.2116	likely_benign	0.2097	benign	-1.39	Destabilizing	0.008	N	0.413	neutral	None	None	None	None	N
V/F	0.1235	likely_benign	0.1213	benign	-1.205	Destabilizing	0.627	D	0.561	neutral	N	0.499215136	None	None	N
V/G	0.2216	likely_benign	0.2355	benign	-1.911	Destabilizing	0.324	N	0.609	neutral	N	0.490826133	None	None	N
V/H	0.3453	ambiguous	0.3307	benign	-1.488	Destabilizing	0.981	D	0.617	neutral	None	None	None	None	N
V/I	0.0679	likely_benign	0.0642	benign	-0.682	Destabilizing	0.001	N	0.133	neutral	N	0.447053926	None	None	N
V/K	0.1683	likely_benign	0.1608	benign	-1.149	Destabilizing	0.388	N	0.582	neutral	None	None	None	None	N
V/L	0.1666	likely_benign	0.1539	benign	-0.682	Destabilizing	0.033	N	0.409	neutral	D	0.528901731	None	None	N
V/M	0.1046	likely_benign	0.0972	benign	-0.607	Destabilizing	0.69	D	0.5	neutral	None	None	None	None	N
V/N	0.2027	likely_benign	0.1943	benign	-1.036	Destabilizing	0.69	D	0.627	neutral	None	None	None	None	N
V/P	0.8988	likely_pathogenic	0.9167	pathogenic	-0.941	Destabilizing	0.818	D	0.596	neutral	None	None	None	None	N
V/Q	0.2057	likely_benign	0.2007	benign	-1.171	Destabilizing	0.69	D	0.601	neutral	None	None	None	None	N
V/R	0.1441	likely_benign	0.1442	benign	-0.73	Destabilizing	0.69	D	0.637	neutral	None	None	None	None	N
V/S	0.1799	likely_benign	0.1806	benign	-1.623	Destabilizing	0.241	N	0.559	neutral	None	None	None	None	N
V/T	0.1126	likely_benign	0.1075	benign	-1.472	Destabilizing	0.008	N	0.306	neutral	None	None	None	None	N
V/W	0.6433	likely_pathogenic	0.6204	pathogenic	-1.433	Destabilizing	0.981	D	0.657	neutral	None	None	None	None	N
V/Y	0.3622	ambiguous	0.3475	ambiguous	-1.102	Destabilizing	0.818	D	0.566	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.