TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9010	27253;27254;27255	chr2:178713106;178713105;178713104	chr2:179577833;179577832;179577831
N2AB	8693	26302;26303;26304	chr2:178713106;178713105;178713104	chr2:179577833;179577832;179577831
N2A	7766	23521;23522;23523	chr2:178713106;178713105;178713104	chr2:179577833;179577832;179577831
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-75
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.3562
• 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
S/G	None	None	None	D	0.213	0.184	0.168933306366	gnomAD-4.0.0	1.36867E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7992E-06	0	0
S/R	rs774115714	-0.333	0.295	N	0.624	0.121	0.277317399466	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
S/R	rs774115714	-0.333	0.295	N	0.624	0.121	0.277317399466	gnomAD-4.0.0	6.36809E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.1439E-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
S/A	0.0911	likely_benign	0.0944	benign	-0.536	Destabilizing	None	N	0.216	neutral	None	None	None	None	N
S/C	0.1341	likely_benign	0.1626	benign	-0.302	Destabilizing	None	N	0.325	neutral	D	0.544973207	None	None	N
S/D	0.3412	ambiguous	0.4019	ambiguous	-0.334	Destabilizing	None	N	0.224	neutral	None	None	None	None	N
S/E	0.3679	ambiguous	0.4266	ambiguous	-0.396	Destabilizing	0.038	N	0.459	neutral	None	None	None	None	N
S/F	0.1452	likely_benign	0.1637	benign	-0.913	Destabilizing	0.214	N	0.676	prob.neutral	None	None	None	None	N
S/G	0.0954	likely_benign	0.108	benign	-0.718	Destabilizing	None	N	0.213	neutral	D	0.543705759	None	None	N
S/H	0.158	likely_benign	0.1891	benign	-1.282	Destabilizing	0.628	D	0.597	neutral	None	None	None	None	N
S/I	0.1236	likely_benign	0.1467	benign	-0.174	Destabilizing	0.295	N	0.687	prob.neutral	N	0.510966742	None	None	N
S/K	0.2377	likely_benign	0.3008	benign	-0.72	Destabilizing	0.072	N	0.474	neutral	None	None	None	None	N
S/L	0.1003	likely_benign	0.1107	benign	-0.174	Destabilizing	0.072	N	0.597	neutral	None	None	None	None	N
S/M	0.1849	likely_benign	0.2033	benign	0.228	Stabilizing	0.628	D	0.597	neutral	None	None	None	None	N
S/N	0.1192	likely_benign	0.1484	benign	-0.481	Destabilizing	0.029	N	0.498	neutral	N	0.499090231	None	None	N
S/P	0.5649	likely_pathogenic	0.5984	pathogenic	-0.263	Destabilizing	0.356	N	0.619	neutral	None	None	None	None	N
S/Q	0.2584	likely_benign	0.3076	benign	-0.759	Destabilizing	0.356	N	0.554	neutral	None	None	None	None	N
S/R	0.1565	likely_benign	0.1953	benign	-0.488	Destabilizing	0.295	N	0.624	neutral	N	0.488872788	None	None	N
S/T	0.0716	likely_benign	0.0785	benign	-0.531	Destabilizing	0.024	N	0.449	neutral	N	0.507873098	None	None	N
S/V	0.1548	likely_benign	0.1679	benign	-0.263	Destabilizing	0.072	N	0.616	neutral	None	None	None	None	N
S/W	0.2809	likely_benign	0.3047	benign	-0.89	Destabilizing	0.001	N	0.516	neutral	None	None	None	None	N
S/Y	0.1554	likely_benign	0.1777	benign	-0.641	Destabilizing	0.214	N	0.675	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.