TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17514	52765;52766;52767	chr2:178608343;178608342;178608341	chr2:179473070;179473069;179473068
N2AB	15873	47842;47843;47844	chr2:178608343;178608342;178608341	chr2:179473070;179473069;179473068
N2A	14946	45061;45062;45063	chr2:178608343;178608342;178608341	chr2:179473070;179473069;179473068
N2B	8449	25570;25571;25572	chr2:178608343;178608342;178608341	chr2:179473070;179473069;179473068
Novex-1	8574	25945;25946;25947	chr2:178608343;178608342;178608341	chr2:179473070;179473069;179473068
Novex-2	8641	26146;26147;26148	chr2:178608343;178608342;178608341	chr2:179473070;179473069;179473068
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-15
• Domain position: 45
• Structural Position: 63
• Q(SASA): 0.7568
• 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
T/I	None	None	0.997	N	0.357	0.441	0.386558576397	gnomAD-4.0.0	1.3696E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79979E-06	0	0
T/P	rs1470590917	None	0.997	N	0.359	0.334	0.333906830038	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	2.88018E-04	0	None	0	0	0	0	0
T/P	rs1470590917	None	0.997	N	0.359	0.334	0.333906830038	gnomAD-4.0.0	6.58025E-06	None	None	None	None	N	None	0	0	None	2.88018E-04	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
T/A	0.1177	likely_benign	0.109	benign	-0.226	Destabilizing	0.911	D	0.347	neutral	N	0.462222874	None	None	N
T/C	0.6628	likely_pathogenic	0.5893	pathogenic	-0.3	Destabilizing	1.0	D	0.4	neutral	None	None	None	None	N
T/D	0.6983	likely_pathogenic	0.5753	pathogenic	0.085	Stabilizing	0.985	D	0.326	neutral	None	None	None	None	N
T/E	0.6016	likely_pathogenic	0.4887	ambiguous	-0.003	Destabilizing	0.985	D	0.347	neutral	None	None	None	None	N
T/F	0.5449	ambiguous	0.4634	ambiguous	-0.867	Destabilizing	0.999	D	0.488	neutral	None	None	None	None	N
T/G	0.3446	ambiguous	0.2886	benign	-0.3	Destabilizing	0.985	D	0.377	neutral	None	None	None	None	N
T/H	0.4438	ambiguous	0.3838	ambiguous	-0.463	Destabilizing	1.0	D	0.5	neutral	None	None	None	None	N
T/I	0.2916	likely_benign	0.2593	benign	-0.154	Destabilizing	0.997	D	0.357	neutral	N	0.451603236	None	None	N
T/K	0.2684	likely_benign	0.2263	benign	-0.266	Destabilizing	0.98	D	0.326	neutral	N	0.40261721	None	None	N
T/L	0.1571	likely_benign	0.1337	benign	-0.154	Destabilizing	0.993	D	0.345	neutral	None	None	None	None	N
T/M	0.1383	likely_benign	0.1313	benign	-0.141	Destabilizing	1.0	D	0.365	neutral	None	None	None	None	N
T/N	0.2138	likely_benign	0.1918	benign	-0.043	Destabilizing	0.985	D	0.287	neutral	None	None	None	None	N
T/P	0.1591	likely_benign	0.1316	benign	-0.153	Destabilizing	0.997	D	0.359	neutral	N	0.455680904	None	None	N
T/Q	0.3349	likely_benign	0.2931	benign	-0.253	Destabilizing	0.998	D	0.354	neutral	None	None	None	None	N
T/R	0.2921	likely_benign	0.2444	benign	0.036	Stabilizing	0.997	D	0.361	neutral	N	0.4460427	None	None	N
T/S	0.1589	likely_benign	0.1398	benign	-0.222	Destabilizing	0.449	N	0.175	neutral	N	0.407292311	None	None	N
T/V	0.2181	likely_benign	0.1949	benign	-0.153	Destabilizing	0.993	D	0.311	neutral	None	None	None	None	N
T/W	0.8239	likely_pathogenic	0.7562	pathogenic	-0.939	Destabilizing	1.0	D	0.602	neutral	None	None	None	None	N
T/Y	0.5597	ambiguous	0.4674	ambiguous	-0.622	Destabilizing	0.999	D	0.485	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.