TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30478	91657;91658;91659	chr2:178551099;178551098;178551097	chr2:179415826;179415825;179415824
N2AB	28837	86734;86735;86736	chr2:178551099;178551098;178551097	chr2:179415826;179415825;179415824
N2A	27910	83953;83954;83955	chr2:178551099;178551098;178551097	chr2:179415826;179415825;179415824
N2B	21413	64462;64463;64464	chr2:178551099;178551098;178551097	chr2:179415826;179415825;179415824
Novex-1	21538	64837;64838;64839	chr2:178551099;178551098;178551097	chr2:179415826;179415825;179415824
Novex-2	21605	65038;65039;65040	chr2:178551099;178551098;178551097	chr2:179415826;179415825;179415824
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: Fn3-110
• Domain position: 57
• Structural Position: 88
• Q(SASA): 0.3941
• Predicted PPI site: I

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/D	rs373900294	-0.411	0.016	N	0.227	0.032	0.141422826196	gnomAD-2.1.1	2.51E-05	None	None	None	None	I	None	2.48283E-04	0	None	0	0	None	0	None	0	0	1.41004E-04
E/D	rs373900294	-0.411	0.016	N	0.227	0.032	0.141422826196	gnomAD-3.1.2	1.05168E-04	None	None	None	None	I	None	2.65508E-04	2.6202E-04	0	0	0	None	0	0	0	0	4.77555E-04
E/D	rs373900294	-0.411	0.016	N	0.227	0.032	0.141422826196	gnomAD-4.0.0	1.42561E-05	None	None	None	None	I	None	2.27018E-04	8.33806E-05	None	0	0	None	0	0	0	0	1.60133E-05
E/V	rs794729531	0.288	0.973	N	0.765	0.473	0.481246930725	gnomAD-2.1.1	2.02E-05	None	None	None	None	I	None	0	1.45307E-04	None	0	0	None	0	None	0	0	0
E/V	rs794729531	0.288	0.973	N	0.765	0.473	0.481246930725	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	1.31079E-04	0	0	0	None	0	0	0	0	0
E/V	rs794729531	0.288	0.973	N	0.765	0.473	0.481246930725	gnomAD-4.0.0	1.02532E-05	None	None	None	None	I	None	0	1.35653E-04	None	0	0	None	0	0	0	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
E/A	0.186	likely_benign	0.231	benign	-0.124	Destabilizing	0.834	D	0.677	prob.neutral	N	0.449832367	None	None	I
E/C	0.8681	likely_pathogenic	0.893	pathogenic	-0.202	Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	I
E/D	0.0865	likely_benign	0.091	benign	-0.36	Destabilizing	0.016	N	0.227	neutral	N	0.394536445	None	None	I
E/F	0.8209	likely_pathogenic	0.8615	pathogenic	0.09	Stabilizing	0.998	D	0.749	deleterious	None	None	None	None	I
E/G	0.2287	likely_benign	0.2579	benign	-0.321	Destabilizing	0.946	D	0.685	prob.neutral	N	0.469303562	None	None	I
E/H	0.5593	ambiguous	0.6261	pathogenic	0.549	Stabilizing	0.998	D	0.714	prob.delet.	None	None	None	None	I
E/I	0.4514	ambiguous	0.5348	ambiguous	0.359	Stabilizing	0.979	D	0.779	deleterious	None	None	None	None	I
E/K	0.316	likely_benign	0.3721	ambiguous	0.393	Stabilizing	0.834	D	0.601	neutral	N	0.462145516	None	None	I
E/L	0.5104	ambiguous	0.5938	pathogenic	0.359	Stabilizing	0.979	D	0.779	deleterious	None	None	None	None	I
E/M	0.5765	likely_pathogenic	0.6553	pathogenic	0.168	Stabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	I
E/N	0.2326	likely_benign	0.272	benign	-0.043	Destabilizing	0.921	D	0.73	prob.delet.	None	None	None	None	I
E/P	0.8762	likely_pathogenic	0.9052	pathogenic	0.219	Stabilizing	0.979	D	0.794	deleterious	None	None	None	None	I
E/Q	0.211	likely_benign	0.2436	benign	0.02	Stabilizing	0.946	D	0.662	neutral	N	0.458894567	None	None	I
E/R	0.4757	ambiguous	0.5336	ambiguous	0.711	Stabilizing	0.979	D	0.74	deleterious	None	None	None	None	I
E/S	0.1981	likely_benign	0.2342	benign	-0.179	Destabilizing	0.769	D	0.638	neutral	None	None	None	None	I
E/T	0.2428	likely_benign	0.2897	benign	-0.008	Destabilizing	0.959	D	0.751	deleterious	None	None	None	None	I
E/V	0.2853	likely_benign	0.3555	ambiguous	0.219	Stabilizing	0.973	D	0.765	deleterious	N	0.454662184	None	None	I
E/W	0.9483	likely_pathogenic	0.9633	pathogenic	0.227	Stabilizing	0.998	D	0.745	deleterious	None	None	None	None	I
E/Y	0.6998	likely_pathogenic	0.7566	pathogenic	0.34	Stabilizing	0.998	D	0.75	deleterious	None	None	None	None	I

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.