TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23684	71275;71276;71277	chr2:178575082;178575081;178575080	chr2:179439809;179439808;179439807
N2AB	22043	66352;66353;66354	chr2:178575082;178575081;178575080	chr2:179439809;179439808;179439807
N2A	21116	63571;63572;63573	chr2:178575082;178575081;178575080	chr2:179439809;179439808;179439807
N2B	14619	44080;44081;44082	chr2:178575082;178575081;178575080	chr2:179439809;179439808;179439807
Novex-1	14744	44455;44456;44457	chr2:178575082;178575081;178575080	chr2:179439809;179439808;179439807
Novex-2	14811	44656;44657;44658	chr2:178575082;178575081;178575080	chr2:179439809;179439808;179439807
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-130
• Domain position: 48
• Structural Position: 127
• Q(SASA): 0.4
• 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	0.001	N	0.384	0.126	0.210429274316	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-06	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	0.0748	likely_benign	0.074	benign	-0.761	Destabilizing	0.005	N	0.312	neutral	N	0.4857456	None	None	N
T/C	0.215	likely_benign	0.2345	benign	-0.391	Destabilizing	0.676	D	0.501	neutral	None	None	None	None	N
T/D	0.1579	likely_benign	0.1654	benign	0.116	Stabilizing	0.016	N	0.475	neutral	None	None	None	None	N
T/E	0.2085	likely_benign	0.2043	benign	0.089	Stabilizing	0.016	N	0.474	neutral	None	None	None	None	N
T/F	0.2127	likely_benign	0.2162	benign	-1.034	Destabilizing	0.356	N	0.57	neutral	None	None	None	None	N
T/G	0.167	likely_benign	0.174	benign	-0.973	Destabilizing	0.016	N	0.557	neutral	None	None	None	None	N
T/H	0.1248	likely_benign	0.1285	benign	-1.338	Destabilizing	0.214	N	0.557	neutral	None	None	None	None	N
T/I	0.1272	likely_benign	0.1286	benign	-0.298	Destabilizing	0.001	N	0.384	neutral	N	0.499253615	None	None	N
T/K	0.1738	likely_benign	0.163	benign	-0.514	Destabilizing	0.016	N	0.498	neutral	None	None	None	None	N
T/L	0.0979	likely_benign	0.0979	benign	-0.298	Destabilizing	0.016	N	0.481	neutral	None	None	None	None	N
T/M	0.0929	likely_benign	0.0913	benign	0.062	Stabilizing	0.356	N	0.511	neutral	None	None	None	None	N
T/N	0.0447	likely_benign	0.0471	benign	-0.373	Destabilizing	None	N	0.278	neutral	N	0.415789656	None	None	N
T/P	0.1699	likely_benign	0.1583	benign	-0.421	Destabilizing	0.055	N	0.522	neutral	N	0.478051623	None	None	N
T/Q	0.1699	likely_benign	0.1627	benign	-0.581	Destabilizing	0.072	N	0.523	neutral	None	None	None	None	N
T/R	0.1662	likely_benign	0.1527	benign	-0.319	Destabilizing	None	N	0.379	neutral	None	None	None	None	N
T/S	0.0737	likely_benign	0.0769	benign	-0.685	Destabilizing	None	N	0.305	neutral	N	0.463274172	None	None	N
T/V	0.1039	likely_benign	0.1061	benign	-0.421	Destabilizing	0.016	N	0.352	neutral	None	None	None	None	N
T/W	0.4917	ambiguous	0.4834	ambiguous	-0.948	Destabilizing	0.864	D	0.563	neutral	None	None	None	None	N
T/Y	0.1377	likely_benign	0.1436	benign	-0.7	Destabilizing	0.356	N	0.571	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.