Submissions for variant NM_000321.3(RB1):c.1695+30914_1695+30917dup

dbSNP: rs558917628

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001823308	SCV002072798	pathogenic	not provided	2022-01-26	criteria provided, single submitter	clinical testing	Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 321 amino acids are lost and replaced with 28 incorrect amino acids (HGMD); This variant is associated with the following publications: (PMID: 22385360, 18297072, 28425126, 21426374)
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV001783609	SCV002761192	pathogenic	Hypotrichosis 8	2022-11-24	criteria provided, single submitter	clinical testing	A homozygous 4 base pair duplication in exon 1 of the LPAR6 gene that results in a frameshift and premature truncation of the protein 29 amino acids downstream to codon 24 was detected.This variant has not been reported in the 1000 genomes and gnomAD databases. The reference region is conserved across species. In summary, the variant meets our criteria to be classified as pathogenic.
Neuberg Centre For Genomic Medicine, NCGM	RCV001783609	SCV004176596	pathogenic	Hypotrichosis 8	2023-03-01	criteria provided, single submitter	clinical testing	The frameshift variant c.66_69dup(p.Phe24HisfsTer29) in LPAR6 gene has been reported previously in homozygous state in multiple individuals with woolly hair and/or hypotrichosis. This variant is considered to have a founder effect in Pakistani patients (Kurban M, et al., 2013, Khan S, et al., 2011). The variant has 0.005% allele frequency in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant causes a frameshift starting with codon Phenylalanine 24, changes this amino acid to Histidine residue, and creates a premature Stop codon at position 29 of the new reading frame, denoted p.Phe24HisfsTer29. This variant has been reported to the ClinVar database as Pathogenic. This frameshift variant in the C-terminus is predicted to result in protein truncation, as the last 321 amino acids are lost and replaced with 28 incorrect amino acids. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV002273832	SCV000022056	pathogenic	Wooly hair, autosomal recessive 1, with or without hypotrichosis	2011-08-01	no assertion criteria provided	literature only
OMIM	RCV001783609	SCV000045050	pathogenic	Hypotrichosis 8	2011-08-01	no assertion criteria provided	literature only
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV001783609	SCV002319211	pathogenic	Hypotrichosis 8		no assertion criteria provided	clinical testing