Submissions for variant NM_031220.4(PITPNM3):c.1878G>C (p.Gln626His)

gnomAD frequency: 0.00212  dbSNP: rs76024428

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000512878	SCV000203255	uncertain significance	not provided	2015-02-20	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000002071	SCV000405823	benign	Cone-rod dystrophy 5	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV000512878	SCV000608801	likely pathogenic	not provided	2017-04-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000153697	SCV000730655	likely benign	not specified	2017-10-19	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Mayo Clinic Laboratories, Mayo Clinic	RCV000002071	SCV000782437	uncertain significance	Cone-rod dystrophy 5	2016-04-01	criteria provided, single submitter	clinical testing
Invitae	RCV000512878	SCV001099581	likely benign	not provided	2024-01-25	criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV000002071	SCV002769125	likely benign	Cone-rod dystrophy 5	2020-05-21	criteria provided, single submitter	clinical testing	A heterozygous missense variant was identified, NM_031220.3(PITPNM3):c.1878G>C in exon 14 of the PITPNM3 gene. This substitution is predicted to create a minor amino acid change from a glutamine to a histidine at position 626 of the protein; NP_112497.2(PITPNM3):p.(Gln626His). The glutamine at this position has low conservation (100 vertebrates, UCSC), and is not situated in a known functional domain (NCBI, PDB). In silico software predicts this variant to be tolerated (PolyPhen2, PROVEAN, MutationAssessor, FATHMM). The variant is present in the gnomAD population database at a global population frequency of 0.16% (455 heterozygotes, 0 homozygotes) with a European sub-population frequency of 0.31%. This variant has been previously reported with conflicting interpretations of pathogenicity in patients with cone-rod dystrophy (ClinVar, Reinis A. et al. (2013), Zhao, L. et al (2015), Khan, K. et al (2017), Jespersgaard, C. et al. (2019)). Based on information available at the time of curation, this variant has been classified as LIKELY BENIGN.
PreventionGenetics, part of Exact Sciences	RCV003934792	SCV004752112	likely benign	PITPNM3-related disorder	2020-02-14	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
OMIM	RCV000002071	SCV000022229	pathogenic	Cone-rod dystrophy 5	2007-06-01	flagged submission	literature only
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787861	SCV000926877	uncertain significance	Retinitis pigmentosa	2018-04-01	no assertion criteria provided	research