TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9939	30040;30041;30042	chr2:178704657;178704656;178704655	chr2:179569384;179569383;179569382
N2AB	9622	29089;29090;29091	chr2:178704657;178704656;178704655	chr2:179569384;179569383;179569382
N2A	8695	26308;26309;26310	chr2:178704657;178704656;178704655	chr2:179569384;179569383;179569382
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-84
• Domain position: 40
• Structural Position: 55
• Q(SASA): 0.5086
• 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
E/Q	rs727503638	0.144	0.003	None	0.136	0.149	0.216624796971	gnomAD-2.1.1	1.22E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.91E-05	None	0	0	0
E/Q	rs727503638	0.144	0.003	None	0.136	0.149	0.216624796971	gnomAD-4.0.0	6.84983E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16187E-04	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
E/A	0.1699	likely_benign	0.2174	benign	-0.596	Destabilizing	0.09	N	0.339	neutral	None	None	None	None	N
E/C	0.8865	likely_pathogenic	0.9276	pathogenic	-0.315	Destabilizing	0.944	D	0.509	neutral	None	None	None	None	N
E/D	0.304	likely_benign	0.3755	ambiguous	-0.59	Destabilizing	0.324	N	0.374	neutral	None	None	None	None	N
E/F	0.7555	likely_pathogenic	0.8568	pathogenic	-0.128	Destabilizing	0.69	D	0.475	neutral	None	None	None	None	N
E/G	0.3141	likely_benign	0.4101	ambiguous	-0.862	Destabilizing	0.324	N	0.421	neutral	None	None	None	None	N
E/H	0.545	ambiguous	0.6171	pathogenic	0.101	Stabilizing	0.818	D	0.365	neutral	None	None	None	None	N
E/I	0.1744	likely_benign	0.3136	benign	0.099	Stabilizing	0.098	N	0.437	neutral	None	None	None	None	N
E/K	0.1385	likely_benign	0.1673	benign	0.113	Stabilizing	0.09	N	0.392	neutral	None	None	None	None	N
E/L	0.353	ambiguous	0.457	ambiguous	0.099	Stabilizing	0.241	N	0.405	neutral	None	None	None	None	N
E/M	0.3273	likely_benign	0.4582	ambiguous	0.185	Stabilizing	0.69	D	0.445	neutral	None	None	None	None	N
E/N	0.344	ambiguous	0.4374	ambiguous	-0.512	Destabilizing	0.388	N	0.371	neutral	None	None	None	None	N
E/P	0.9647	likely_pathogenic	0.9775	pathogenic	-0.112	Destabilizing	0.818	D	0.383	neutral	None	None	None	None	N
E/Q	0.1046	likely_benign	0.0799	benign	-0.411	Destabilizing	0.003	N	0.136	neutral	None	None	None	None	N
E/R	0.2312	likely_benign	0.2781	benign	0.452	Stabilizing	0.241	N	0.362	neutral	None	None	None	None	N
E/S	0.2558	likely_benign	0.3315	benign	-0.654	Destabilizing	0.388	N	0.337	neutral	None	None	None	None	N
E/T	0.1884	likely_benign	0.2604	benign	-0.423	Destabilizing	0.241	N	0.339	neutral	None	None	None	None	N
E/V	0.1085	likely_benign	0.18	benign	-0.112	Destabilizing	0.001	N	0.274	neutral	None	None	None	None	N
E/W	0.925	likely_pathogenic	0.9567	pathogenic	0.147	Stabilizing	0.981	D	0.53	neutral	None	None	None	None	N
E/Y	0.7351	likely_pathogenic	0.8181	pathogenic	0.143	Stabilizing	0.818	D	0.455	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.