TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8120	24583;24584;24585	chr2:178718842;178718841;178718840	chr2:179583569;179583568;179583567
N2AB	7803	23632;23633;23634	chr2:178718842;178718841;178718840	chr2:179583569;179583568;179583567
N2A	6876	20851;20852;20853	chr2:178718842;178718841;178718840	chr2:179583569;179583568;179583567
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-66
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.4626
• 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
P/L	None	None	0.024	D	0.364	0.223	0.52535981233	gnomAD-4.0.0	6.15809E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09546E-06	0	0
P/S	rs745913661	-0.074	None	N	0.117	0.119	0.0551355673512	gnomAD-2.1.1	4.83E-05	None	None	None	None	N	None	0	0	None	0	6.69195E-04	None	0	None	0	0	0
P/S	rs745913661	-0.074	None	N	0.117	0.119	0.0551355673512	gnomAD-4.0.0	3.2843E-05	None	None	None	None	N	None	0	0	None	0	1.20968E-03	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
P/A	0.0595	likely_benign	0.0574	benign	-0.438	Destabilizing	None	N	0.144	neutral	N	0.513009559	None	None	N
P/C	0.3062	likely_benign	0.3101	benign	-0.657	Destabilizing	0.001	N	0.279	neutral	None	None	None	None	N
P/D	0.2705	likely_benign	0.2598	benign	-0.361	Destabilizing	0.038	N	0.327	neutral	None	None	None	None	N
P/E	0.1687	likely_benign	0.1586	benign	-0.479	Destabilizing	0.016	N	0.333	neutral	None	None	None	None	N
P/F	0.2676	likely_benign	0.2712	benign	-0.727	Destabilizing	0.356	N	0.397	neutral	None	None	None	None	N
P/G	0.1642	likely_benign	0.1612	benign	-0.55	Destabilizing	0.016	N	0.333	neutral	None	None	None	None	N
P/H	0.1247	likely_benign	0.1241	benign	-0.131	Destabilizing	0.171	N	0.354	neutral	N	0.518436808	None	None	N
P/I	0.2083	likely_benign	0.2067	benign	-0.294	Destabilizing	0.072	N	0.435	neutral	None	None	None	None	N
P/K	0.1616	likely_benign	0.1529	benign	-0.423	Destabilizing	0.038	N	0.335	neutral	None	None	None	None	N
P/L	0.0909	likely_benign	0.0886	benign	-0.294	Destabilizing	0.024	N	0.364	neutral	D	0.526074857	None	None	N
P/M	0.1921	likely_benign	0.1898	benign	-0.408	Destabilizing	0.356	N	0.365	neutral	None	None	None	None	N
P/N	0.1933	likely_benign	0.1881	benign	-0.172	Destabilizing	0.038	N	0.357	neutral	None	None	None	None	N
P/Q	0.1049	likely_benign	0.0969	benign	-0.418	Destabilizing	None	N	0.205	neutral	None	None	None	None	N
P/R	0.111	likely_benign	0.1087	benign	0.093	Stabilizing	0.029	N	0.379	neutral	N	0.484149074	None	None	N
P/S	0.0716	likely_benign	0.0695	benign	-0.501	Destabilizing	None	N	0.117	neutral	N	0.429505528	None	None	N
P/T	0.0713	likely_benign	0.0705	benign	-0.519	Destabilizing	0.001	N	0.17	neutral	N	0.509411893	None	None	N
P/V	0.1619	likely_benign	0.1547	benign	-0.308	Destabilizing	0.072	N	0.356	neutral	None	None	None	None	N
P/W	0.3337	likely_benign	0.3329	benign	-0.799	Destabilizing	0.864	D	0.405	neutral	None	None	None	None	N
P/Y	0.2385	likely_benign	0.2375	benign	-0.5	Destabilizing	0.356	N	0.399	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.