TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29994	90205;90206;90207	chr2:178552920;178552919;178552918	chr2:179417647;179417646;179417645
N2AB	28353	85282;85283;85284	chr2:178552920;178552919;178552918	chr2:179417647;179417646;179417645
N2A	27426	82501;82502;82503	chr2:178552920;178552919;178552918	chr2:179417647;179417646;179417645
N2B	20929	63010;63011;63012	chr2:178552920;178552919;178552918	chr2:179417647;179417646;179417645
Novex-1	21054	63385;63386;63387	chr2:178552920;178552919;178552918	chr2:179417647;179417646;179417645
Novex-2	21121	63586;63587;63588	chr2:178552920;178552919;178552918	chr2:179417647;179417646;179417645
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-106
• Domain position: 62
• Structural Position: 93
• Q(SASA): 0.0728
• 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
L/P	rs1334681258	-1.327	0.741	N	0.845	0.442	0.684753540027	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
L/P	rs1334681258	-1.327	0.741	N	0.845	0.442	0.684753540027	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
L/P	rs1334681258	-1.327	0.741	N	0.845	0.442	0.684753540027	gnomAD-4.0.0	3.84359E-06	None	None	None	None	N	None	0	1.6952E-05	None	0	0	None	0	0	2.39284E-06	0	2.84382E-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
L/A	0.373	ambiguous	0.3194	benign	-2.173	Highly Destabilizing	0.035	N	0.71	prob.delet.	None	None	None	None	N
L/C	0.4823	ambiguous	0.4219	ambiguous	-1.544	Destabilizing	0.824	D	0.803	deleterious	None	None	None	None	N
L/D	0.9192	likely_pathogenic	0.8827	pathogenic	-2.509	Highly Destabilizing	0.555	D	0.843	deleterious	None	None	None	None	N
L/E	0.7603	likely_pathogenic	0.7044	pathogenic	-2.212	Highly Destabilizing	0.555	D	0.807	deleterious	None	None	None	None	N
L/F	0.2154	likely_benign	0.174	benign	-1.333	Destabilizing	0.38	N	0.753	deleterious	None	None	None	None	N
L/G	0.7365	likely_pathogenic	0.6379	pathogenic	-2.747	Highly Destabilizing	0.555	D	0.803	deleterious	None	None	None	None	N
L/H	0.6042	likely_pathogenic	0.5627	ambiguous	-2.392	Highly Destabilizing	0.935	D	0.839	deleterious	None	None	None	None	N
L/I	0.062	likely_benign	0.0551	benign	-0.479	Destabilizing	None	N	0.255	neutral	N	0.347825507	None	None	N
L/K	0.7322	likely_pathogenic	0.7016	pathogenic	-1.66	Destabilizing	0.555	D	0.805	deleterious	None	None	None	None	N
L/M	0.1143	likely_benign	0.1088	benign	-0.59	Destabilizing	0.38	N	0.678	prob.neutral	None	None	None	None	N
L/N	0.7048	likely_pathogenic	0.6205	pathogenic	-2.245	Highly Destabilizing	0.791	D	0.845	deleterious	None	None	None	None	N
L/P	0.8328	likely_pathogenic	0.7629	pathogenic	-1.03	Destabilizing	0.741	D	0.845	deleterious	N	0.510369112	None	None	N
L/Q	0.5339	ambiguous	0.5065	ambiguous	-1.903	Destabilizing	0.741	D	0.831	deleterious	N	0.501690913	None	None	N
L/R	0.6673	likely_pathogenic	0.6255	pathogenic	-1.803	Destabilizing	0.484	N	0.832	deleterious	N	0.502557705	None	None	N
L/S	0.6461	likely_pathogenic	0.5611	ambiguous	-2.89	Highly Destabilizing	0.149	N	0.794	deleterious	None	None	None	None	N
L/T	0.4064	ambiguous	0.3433	ambiguous	-2.416	Highly Destabilizing	0.081	N	0.785	deleterious	None	None	None	None	N
L/V	0.0586	likely_benign	0.0535	benign	-1.03	Destabilizing	None	N	0.26	neutral	N	0.31047784	None	None	N
L/W	0.5436	ambiguous	0.5028	ambiguous	-1.664	Destabilizing	0.935	D	0.81	deleterious	None	None	None	None	N
L/Y	0.5485	ambiguous	0.4796	ambiguous	-1.361	Destabilizing	0.555	D	0.811	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.