TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14059	42400;42401;42402	chr2:178634606;178634605;178634604	chr2:179499333;179499332;179499331
N2AB	12418	37477;37478;37479	chr2:178634606;178634605;178634604	chr2:179499333;179499332;179499331
N2A	11491	34696;34697;34698	chr2:178634606;178634605;178634604	chr2:179499333;179499332;179499331
N2B	4994	15205;15206;15207	chr2:178634606;178634605;178634604	chr2:179499333;179499332;179499331
Novex-1	5119	15580;15581;15582	chr2:178634606;178634605;178634604	chr2:179499333;179499332;179499331
Novex-2	5186	15781;15782;15783	chr2:178634606;178634605;178634604	chr2:179499333;179499332;179499331
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-91
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5741
• 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/H	rs1173536699	-0.652	1.0	D	0.744	0.425	0.68313252318	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14837E-04	0	None	0	0	None	0	None	0	0	0
P/H	rs1173536699	-0.652	1.0	D	0.744	0.425	0.68313252318	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
P/H	rs1173536699	-0.652	1.0	D	0.744	0.425	0.68313252318	gnomAD-4.0.0	6.58241E-06	None	None	None	None	N	None	2.41756E-05	0	None	0	0	None	0	0	0	0	0
P/L	rs1173536699	-0.182	0.999	N	0.803	0.395	0.778299035629	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	6.51042E-04	None	0	None	0	0	0
P/L	rs1173536699	-0.182	0.999	N	0.803	0.395	0.778299035629	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93798E-04	None	0	0	0	0	0
P/L	rs1173536699	-0.182	0.999	N	0.803	0.395	0.778299035629	gnomAD-4.0.0	6.58241E-06	None	None	None	None	N	None	0	0	None	0	1.93798E-04	None	0	0	0	0	0
P/S	None	None	0.999	D	0.771	0.428	0.478980160563	gnomAD-4.0.0	2.05327E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99685E-07	2.31981E-05	0
P/T	None	None	0.999	D	0.794	0.393	0.619752075125	gnomAD-4.0.0	2.05327E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69906E-06	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	0.1634	likely_benign	0.1571	benign	-1.052	Destabilizing	0.996	D	0.711	prob.delet.	D	0.564340692	None	None	N
P/C	0.8548	likely_pathogenic	0.85	pathogenic	-0.582	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
P/D	0.729	likely_pathogenic	0.7243	pathogenic	-0.593	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
P/E	0.4784	ambiguous	0.4867	ambiguous	-0.602	Destabilizing	0.994	D	0.741	deleterious	None	None	None	None	N
P/F	0.8617	likely_pathogenic	0.8511	pathogenic	-0.751	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
P/G	0.6085	likely_pathogenic	0.6089	pathogenic	-1.342	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
P/H	0.5019	ambiguous	0.4794	ambiguous	-0.816	Destabilizing	1.0	D	0.744	deleterious	D	0.568681982	None	None	N
P/I	0.7443	likely_pathogenic	0.704	pathogenic	-0.374	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
P/K	0.621	likely_pathogenic	0.5783	pathogenic	-0.81	Destabilizing	0.998	D	0.77	deleterious	None	None	None	None	N
P/L	0.3409	ambiguous	0.3128	benign	-0.374	Destabilizing	0.999	D	0.803	deleterious	N	0.508897311	None	None	N
P/M	0.7016	likely_pathogenic	0.6726	pathogenic	-0.318	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
P/N	0.684	likely_pathogenic	0.6606	pathogenic	-0.578	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
P/Q	0.3632	ambiguous	0.3439	ambiguous	-0.72	Destabilizing	0.985	D	0.438	neutral	None	None	None	None	N
P/R	0.4608	ambiguous	0.4324	ambiguous	-0.344	Destabilizing	0.999	D	0.791	deleterious	N	0.504034864	None	None	N
P/S	0.2967	likely_benign	0.2878	benign	-1.092	Destabilizing	0.999	D	0.771	deleterious	D	0.585233177	None	None	N
P/T	0.307	likely_benign	0.2783	benign	-0.99	Destabilizing	0.999	D	0.794	deleterious	D	0.528298738	None	None	N
P/V	0.5891	likely_pathogenic	0.5421	ambiguous	-0.564	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
P/W	0.943	likely_pathogenic	0.9384	pathogenic	-0.934	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
P/Y	0.8372	likely_pathogenic	0.8181	pathogenic	-0.623	Destabilizing	1.0	D	0.765	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.