Submissions for variant NM_015426.5(POC1A):c.784C>T (p.Arg262Trp)

gnomAD frequency: 0.00019  dbSNP: rs146976547

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000194320	SCV000248550	uncertain significance	not specified	2015-08-06	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514178	SCV000610001	uncertain significance	not provided	2017-05-02	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001330671	SCV001522421	uncertain significance	Short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome	2020-05-05	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Pathology and Clinical Laboratory Medicine, King Fahad Medical City	RCV000194320	SCV002073798	likely benign	not specified		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000514178	SCV002309766	uncertain significance	not provided	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 262 of the POC1A protein (p.Arg262Trp). This variant is present in population databases (rs146976547, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with POC1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 211926). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt POC1A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002517119	SCV003748838	uncertain significance	Inborn genetic diseases	2021-08-02	criteria provided, single submitter	clinical testing	The c.784C>T (p.R262W) alteration is located in exon 7 (coding exon 7) of the POC1A gene. This alteration results from a C to T substitution at nucleotide position 784, causing the arginine (R) at amino acid position 262 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.