TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2865	8818;8819;8820	chr2:178770108;178770107;178770106	chr2:179634835;179634834;179634833
N2AB	2865	8818;8819;8820	chr2:178770108;178770107;178770106	chr2:179634835;179634834;179634833
N2A	2865	8818;8819;8820	chr2:178770108;178770107;178770106	chr2:179634835;179634834;179634833
N2B	2819	8680;8681;8682	chr2:178770108;178770107;178770106	chr2:179634835;179634834;179634833
Novex-1	2819	8680;8681;8682	chr2:178770108;178770107;178770106	chr2:179634835;179634834;179634833
Novex-2	2819	8680;8681;8682	chr2:178770108;178770107;178770106	chr2:179634835;179634834;179634833
Novex-3	2865	8818;8819;8820	chr2:178770108;178770107;178770106	chr2:179634835;179634834;179634833

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-18
• Domain position: 71
• Structural Position: 155
• Q(SASA): 0.1309
• 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	rs2091254998	None	0.991	N	0.783	0.286	0.41337360676	gnomAD-4.0.0	2.05219E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69788E-06	0	0
T/R	None	None	0.1	N	0.505	0.307	0.50539470866	gnomAD-4.0.0	6.84064E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99292E-07	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	0.1254	likely_benign	0.141	benign	-1.148	Destabilizing	0.76	D	0.668	neutral	D	0.523358856	None	None	N
T/C	0.4391	ambiguous	0.47	ambiguous	-0.656	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
T/D	0.7578	likely_pathogenic	0.8051	pathogenic	-1.408	Destabilizing	0.986	D	0.779	deleterious	None	None	None	None	N
T/E	0.5221	ambiguous	0.5475	ambiguous	-1.17	Destabilizing	0.953	D	0.752	deleterious	None	None	None	None	N
T/F	0.346	ambiguous	0.3916	ambiguous	-0.698	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	N
T/G	0.4665	ambiguous	0.5539	ambiguous	-1.588	Destabilizing	0.953	D	0.765	deleterious	None	None	None	None	N
T/H	0.3219	likely_benign	0.3495	ambiguous	-1.555	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
T/I	0.1834	likely_benign	0.1913	benign	0.026	Stabilizing	0.991	D	0.783	deleterious	N	0.454959533	None	None	N
T/K	0.2706	likely_benign	0.2757	benign	-0.223	Destabilizing	0.885	D	0.752	deleterious	N	0.476722425	None	None	N
T/L	0.1455	likely_benign	0.1568	benign	0.026	Stabilizing	0.953	D	0.751	deleterious	None	None	None	None	N
T/M	0.0973	likely_benign	0.1009	benign	-0.096	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
T/N	0.2735	likely_benign	0.315	benign	-1.002	Destabilizing	0.986	D	0.693	prob.neutral	None	None	None	None	N
T/P	0.8995	likely_pathogenic	0.9253	pathogenic	-0.336	Destabilizing	0.997	D	0.783	deleterious	D	0.62988203	None	None	N
T/Q	0.298	likely_benign	0.3188	benign	-0.706	Destabilizing	0.986	D	0.787	deleterious	None	None	None	None	N
T/R	0.2024	likely_benign	0.2158	benign	-0.547	Destabilizing	0.1	N	0.505	neutral	N	0.4790795	None	None	N
T/S	0.1618	likely_benign	0.1881	benign	-1.259	Destabilizing	0.374	N	0.475	neutral	N	0.458846457	None	None	N
T/V	0.1354	likely_benign	0.1373	benign	-0.336	Destabilizing	0.976	D	0.687	prob.neutral	None	None	None	None	N
T/W	0.7091	likely_pathogenic	0.7392	pathogenic	-0.866	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
T/Y	0.4364	ambiguous	0.4584	ambiguous	-0.464	Destabilizing	0.998	D	0.823	deleterious	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.