TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14157	42694;42695;42696	chr2:178634030;178634029;178634028	chr2:179498757;179498756;179498755
N2AB	12516	37771;37772;37773	chr2:178634030;178634029;178634028	chr2:179498757;179498756;179498755
N2A	11589	34990;34991;34992	chr2:178634030;178634029;178634028	chr2:179498757;179498756;179498755
N2B	5092	15499;15500;15501	chr2:178634030;178634029;178634028	chr2:179498757;179498756;179498755
Novex-1	5217	15874;15875;15876	chr2:178634030;178634029;178634028	chr2:179498757;179498756;179498755
Novex-2	5284	16075;16076;16077	chr2:178634030;178634029;178634028	chr2:179498757;179498756;179498755
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-92
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.2872
• 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/G	None	None	None	N	0.256	0.1	0.219573609325	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	3.66327E-05
E/K	rs1207534553	None	0.001	N	0.155	0.105	0.0666544352282	gnomAD-4.0.0	1.59247E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.027E-05

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	0.1598	likely_benign	0.1837	benign	-0.572	Destabilizing	0.027	N	0.361	neutral	N	0.462991925	None	None	N
E/C	0.829	likely_pathogenic	0.8608	pathogenic	-0.135	Destabilizing	0.935	D	0.411	neutral	None	None	None	None	N
E/D	0.1586	likely_benign	0.187	benign	-0.595	Destabilizing	0.052	N	0.291	neutral	N	0.454004062	None	None	N
E/F	0.7533	likely_pathogenic	0.796	pathogenic	-0.335	Destabilizing	0.791	D	0.402	neutral	None	None	None	None	N
E/G	0.1254	likely_benign	0.1687	benign	-0.815	Destabilizing	None	N	0.256	neutral	N	0.457856484	None	None	N
E/H	0.4891	ambiguous	0.5196	ambiguous	-0.253	Destabilizing	0.38	N	0.34	neutral	None	None	None	None	N
E/I	0.4715	ambiguous	0.5187	ambiguous	0.049	Stabilizing	0.38	N	0.417	neutral	None	None	None	None	N
E/K	0.1267	likely_benign	0.1342	benign	0.156	Stabilizing	0.001	N	0.155	neutral	N	0.442258058	None	None	N
E/L	0.472	ambiguous	0.4924	ambiguous	0.049	Stabilizing	0.149	N	0.415	neutral	None	None	None	None	N
E/M	0.4106	ambiguous	0.4457	ambiguous	0.247	Stabilizing	0.555	D	0.366	neutral	None	None	None	None	N
E/N	0.2333	likely_benign	0.2511	benign	-0.28	Destabilizing	0.149	N	0.235	neutral	None	None	None	None	N
E/P	0.9666	likely_pathogenic	0.9671	pathogenic	-0.137	Destabilizing	0.262	N	0.379	neutral	None	None	None	None	N
E/Q	0.1164	likely_benign	0.1125	benign	-0.228	Destabilizing	None	N	0.19	neutral	N	0.456783811	None	None	N
E/R	0.2455	likely_benign	0.2739	benign	0.369	Stabilizing	0.081	N	0.248	neutral	None	None	None	None	N
E/S	0.1907	likely_benign	0.2132	benign	-0.439	Destabilizing	0.035	N	0.271	neutral	None	None	None	None	N
E/T	0.2323	likely_benign	0.2595	benign	-0.238	Destabilizing	0.002	N	0.253	neutral	None	None	None	None	N
E/V	0.2902	likely_benign	0.3155	benign	-0.137	Destabilizing	0.117	N	0.369	neutral	D	0.563956635	None	None	N
E/W	0.9107	likely_pathogenic	0.9295	pathogenic	-0.127	Destabilizing	0.935	D	0.429	neutral	None	None	None	None	N
E/Y	0.6377	likely_pathogenic	0.6975	pathogenic	-0.078	Destabilizing	0.555	D	0.381	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.