TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8980	27163;27164;27165	chr2:178713196;178713195;178713194	chr2:179577923;179577922;179577921
N2AB	8663	26212;26213;26214	chr2:178713196;178713195;178713194	chr2:179577923;179577922;179577921
N2A	7736	23431;23432;23433	chr2:178713196;178713195;178713194	chr2:179577923;179577922;179577921
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-75
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2233
• 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	rs777824582	0.441	0.016	N	0.323	0.236	0.486352402194	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.55E-05	None	0	0	0
T/I	rs777824582	0.441	0.016	N	0.323	0.236	0.486352402194	gnomAD-4.0.0	6.15831E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99497E-07	8.11764E-05	1.65667E-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
T/A	0.1042	likely_benign	0.111	benign	-0.384	Destabilizing	0.002	N	0.146	neutral	N	0.503910073	None	None	N
T/C	0.4831	ambiguous	0.4947	ambiguous	-0.421	Destabilizing	0.992	D	0.542	neutral	None	None	None	None	N
T/D	0.5865	likely_pathogenic	0.6027	pathogenic	-1.53	Destabilizing	0.617	D	0.544	neutral	None	None	None	None	N
T/E	0.542	ambiguous	0.5513	ambiguous	-1.524	Destabilizing	0.617	D	0.523	neutral	None	None	None	None	N
T/F	0.2509	likely_benign	0.2551	benign	-0.674	Destabilizing	0.92	D	0.598	neutral	None	None	None	None	N
T/G	0.3908	ambiguous	0.3962	ambiguous	-0.624	Destabilizing	0.447	N	0.537	neutral	None	None	None	None	N
T/H	0.2813	likely_benign	0.286	benign	-1.115	Destabilizing	0.977	D	0.569	neutral	None	None	None	None	N
T/I	0.1363	likely_benign	0.1365	benign	0.162	Stabilizing	0.016	N	0.323	neutral	N	0.458137711	None	None	N
T/K	0.3102	likely_benign	0.3151	benign	-0.681	Destabilizing	0.447	N	0.544	neutral	None	None	None	None	N
T/L	0.1172	likely_benign	0.1129	benign	0.162	Stabilizing	0.25	N	0.476	neutral	None	None	None	None	N
T/M	0.1008	likely_benign	0.1041	benign	0.584	Stabilizing	0.92	D	0.557	neutral	None	None	None	None	N
T/N	0.1688	likely_benign	0.1784	benign	-0.923	Destabilizing	0.379	N	0.517	neutral	N	0.47680083	None	None	N
T/P	0.6961	likely_pathogenic	0.7255	pathogenic	0.012	Stabilizing	0.896	D	0.573	neutral	N	0.484935996	None	None	N
T/Q	0.3414	ambiguous	0.3437	ambiguous	-1.184	Destabilizing	0.85	D	0.579	neutral	None	None	None	None	N
T/R	0.2235	likely_benign	0.2293	benign	-0.405	Destabilizing	0.85	D	0.573	neutral	None	None	None	None	N
T/S	0.1348	likely_benign	0.1377	benign	-0.897	Destabilizing	0.007	N	0.143	neutral	N	0.453115893	None	None	N
T/V	0.1246	likely_benign	0.1213	benign	0.012	Stabilizing	0.25	N	0.47	neutral	None	None	None	None	N
T/W	0.6565	likely_pathogenic	0.6775	pathogenic	-0.773	Destabilizing	0.992	D	0.595	neutral	None	None	None	None	N
T/Y	0.2895	likely_benign	0.3025	benign	-0.412	Destabilizing	0.972	D	0.614	neutral	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.