TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22922	68989;68990;68991	chr2:178577662;178577661;178577660	chr2:179442389;179442388;179442387
N2AB	21281	64066;64067;64068	chr2:178577662;178577661;178577660	chr2:179442389;179442388;179442387
N2A	20354	61285;61286;61287	chr2:178577662;178577661;178577660	chr2:179442389;179442388;179442387
N2B	13857	41794;41795;41796	chr2:178577662;178577661;178577660	chr2:179442389;179442388;179442387
Novex-1	13982	42169;42170;42171	chr2:178577662;178577661;178577660	chr2:179442389;179442388;179442387
Novex-2	14049	42370;42371;42372	chr2:178577662;178577661;178577660	chr2:179442389;179442388;179442387
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-54
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.4876
• 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
A/V	rs367924146	None	0.797	N	0.541	0.199	0.367425347029	gnomAD-4.0.0	2.40066E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-06	6.07533E-05	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
A/C	0.803	likely_pathogenic	0.7434	pathogenic	-0.619	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
A/D	0.9742	likely_pathogenic	0.9437	pathogenic	-0.822	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	I
A/E	0.9533	likely_pathogenic	0.9057	pathogenic	-0.994	Destabilizing	0.998	D	0.778	deleterious	N	0.493827906	None	None	I
A/F	0.805	likely_pathogenic	0.7381	pathogenic	-0.995	Destabilizing	0.991	D	0.84	deleterious	None	None	None	None	I
A/G	0.6094	likely_pathogenic	0.4874	ambiguous	-0.276	Destabilizing	0.979	D	0.654	neutral	N	0.497195267	None	None	I
A/H	0.9371	likely_pathogenic	0.8986	pathogenic	-0.303	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
A/I	0.6303	likely_pathogenic	0.5454	ambiguous	-0.392	Destabilizing	0.18	N	0.461	neutral	None	None	None	None	I
A/K	0.9728	likely_pathogenic	0.9418	pathogenic	-0.618	Destabilizing	0.995	D	0.779	deleterious	None	None	None	None	I
A/L	0.5925	likely_pathogenic	0.4788	ambiguous	-0.392	Destabilizing	0.839	D	0.512	neutral	None	None	None	None	I
A/M	0.6784	likely_pathogenic	0.5598	ambiguous	-0.34	Destabilizing	0.998	D	0.788	deleterious	None	None	None	None	I
A/N	0.8834	likely_pathogenic	0.8224	pathogenic	-0.233	Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	I
A/P	0.9652	likely_pathogenic	0.944	pathogenic	-0.315	Destabilizing	0.998	D	0.79	deleterious	D	0.545826947	None	None	I
A/Q	0.8827	likely_pathogenic	0.8261	pathogenic	-0.582	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	I
A/R	0.9142	likely_pathogenic	0.8525	pathogenic	-0.06	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	I
A/S	0.2956	likely_benign	0.2289	benign	-0.352	Destabilizing	0.979	D	0.64	neutral	N	0.494779412	None	None	I
A/T	0.5086	ambiguous	0.3645	ambiguous	-0.46	Destabilizing	0.988	D	0.785	deleterious	N	0.515352429	None	None	I
A/V	0.3373	likely_benign	0.2612	benign	-0.315	Destabilizing	0.797	D	0.541	neutral	N	0.466671523	None	None	I
A/W	0.973	likely_pathogenic	0.9596	pathogenic	-1.113	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
A/Y	0.9181	likely_pathogenic	0.8788	pathogenic	-0.774	Destabilizing	0.995	D	0.844	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.